Lithium 3-triphenylmethoxy-1-trans-alkenyl-dialkyl alanates

ABSTRACT

This disclosure describes 3-triphenylmethoxy-1-alkynes, 3-triphenylmethoxy-1-trans-alkenyl-dialkyl-alanes, and lithium 3-triphenylmethoxy-1-trans-alkenyl-dialkyl alanates useful as intermediates for the preparation of certain 11-hydroxy- and 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives which possess bronchodilator, hypotensive, and anti-ulcer activity.

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel hydroxy substituted prostanoic acids and derivatives as well as to intermediates and methods for their preparation. These methods embrace novel and useful procedures for the preparation of prostaglandin, E₁, 11-deoxyprostaglandin E₁, 13-dihydroxyprostaglandin E₁, and other known biologically important prostaglandin congeners. The novel compounds of this invention may be represented by the following general formula: ##SPC1##

Wherein n is an integer having the value 1 or 2; R₁ is hydrogen, lower alkoxy, triphenylmethyl, or triphenylmethyl in which one or two of the phenyl rings is substituted with an alkyl or an alkoxy group having up to 3 carbon atoms; R₂ is a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups each having from one to three carbon atoms, a straight chain alkenyl group having from 3 to 10 carbon atoms, a straight chain alkenyl group having from 3 to 10 carbon atoms and substituted with one or two alkyl groups having between them from 2 to 5 carbon atoms, or a straight chain alkynyl group having from 3 to 10 carbon atoms; R₃ is hydroxy or an alkoxy group having from 1 to 12 carbon atoms; Y is a divalent radical selected from the group consisting of those of the formulae: ##EQU1## Z is a divalent radical selected from the group consisting of those of the formulae: ##EQU2## WHEREIN M IS AN INTEGER FROM 3 TO 8, INCLUSIVE, P IS AN INTEGER FROM 2 TO 6 INCLUSIVE, R₄ is an alkyl group having up to 3 carbon atoms, and R₅ is an alkyl group having up to 3 carbon atoms, a fluorine atom, or a phenyl group; R₆ is hydrogen or an alkyl group having up to three carbon atoms; R₇ is hydrogen or an alkyl group having up to 3 carbon atoms; and the moiety -C₁₃ -C₁₄ - is ethylene, trans-vinylene, or cis-vinylene; with the first proviso that when n is 1, R₁ is hydrogen, R₇ is hydrogen, Z is --(CH₂)_(m) -- and -C₁₃ -C₁₄ - is ethylene or trans-vinylene then R₂ does not include a straight chain alkyl group having from 2 to 10 carbon atoms; and with the second proviso that when Z is ##EQU3## R₁ is hydrogen, R₂ is a straight chain alkyl group having from 2 to 10 carbon atoms and R₇ is hydrogen then -C₁₃ -C₁₄ - is ethylene or cis-vinylene; and with the third proviso that when R₆ is alkyl then R₁ is hydrogen; and with the fourth proviso that only one unsaturated bond can be directly adjacent to C₁₅ ; and with the fifth proviso that when R₇ is an alkyl group then the groups attached to the C₈ position may have the 8α-alkyl(8-iso) configuration of the formula: ##EQU4##

Embraced within the scope of the present invention are all the possible optical isomers of the above general formula. Also embraced within the scope of the present invention are the non-toxic, pharmaceutically acceptable salts of the novel compounds of the present invention when R₃ is hydroxy. The cations comprised in these salts include, for example, the non-toxic metal cations such as the sodium ion, potassium ion, calcium ion, and magnesium ion as well as the organic amine cations such as the tri(lower alkyl)amine cations (e.g., triethylamine, triethanolamine) procaine, and the like.

The novel compounds of the present invention are usually obtainable as oils having characteristic absorption spectra. They are relatively insoluble in water but are relatively soluble in common organic solvents such as ethanol, ethyl acetate, dimethylformamide, and the like. The cationic salts of the compounds when R₃ is hydroxy are, in general, white to yellow crystalline solids having characteristic melting points and absorption spectra. They are relatively soluble in water, methanol, and ethanol but are relatively insoluble in benzene, diethyl ether, and petroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which have been obtained from various animal tissues, and which stimulate smooth muscle, lower arterial blood pressure, antagonize epinephrine-induced mobilization of free fatty acids, and have other pharmacological and autopharmacological effects in mammals. See Bergstrom et al., J. Biol. Chem. 238, 3555 (1963) and Horton, Experientia 21, 113 (1965) and references cited therein. All of the so called natural prostaglandins are derivatives of prostanoic acid: ##SPC2##

The hydrogen atoms attached to C-8 and C-12 are in transconfiguration. When the two side-chains (or the C-8 and C-12 hydrogens) are cis to each other, the compounds are referred to as 8-iso prostaglandins. The natural prostaglandins represent only one of the possible optical isomers. The compounds of this invention include all possible optical isomers.

The novel compounds of the present invention may be readily prepared from certain cycloalkenone intermediates which may be represented by the following general formula: ##SPC3##

wherein R'₃ is an alkoxy group having from 1 to 12 carbon atoms; and n and Z are as hereinabove defined.

The cycloalkenone intermediates may be readily prepared from 2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone in accordance with the reaction schemes set forth in Flowsheets A, B, C, I and J. ##SPC4##

wherein m and n are as hereinabove defined and X is iodo or bromo. In accordance with this reaction scheme, the cycloalk-2-en-1-ones (VIII) are developed by first converting 2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone (I) to the sodium enolates thereof by means of sodium hydride in dimethoxyethane and then treating the sodium enolate with an ethyl ω-haloalkanoate (II). There is thus obtained the corresponding 2-carbethoxy-2-(ω-carbethoxyalkyl)cycloalkanone (III) which is then hydrolyzed and decarboxylated to afford the 2-(ω-carboxyalkyl)cycloalkanone (IV). This acid is then esterified with ethanol whereby the 2-(ω-carbethoxyalkyl)cycloalkanone (V) is obtained. The reaction conditions for carrying out the above sequence of reactions are well known in the art. The conversion of the cycloalkanone (V) to the enol acetate (VI) is effected by heating with acetic anhydride in the presence of p-toluenesulfonic acid. Preparation of the enol acetate (VI) usually requires heating for a period of from about eight to thirty-six hours. During this period, it is preferable to allow by-product acetic acid to distill out in order to force the reaction to completion. The bromination of the enol acetates (VI) to the 2-bromocycloalkanones (VII) is preferably carried out in a two phase system as follows. A solution of bromine in chloroform is added to a rapidly stirred mixture of a solution of the enol acetate (VI) in chloroform and an aqueous solution of an acid acceptor such as calcium carbonate or soda ash. This addition is carried out at 0°-5°C. over a period of about half an hour, stirring is continued for an additional period of about half an hour to a few hours, and the product (VII) is then isolated by standard procedures. The dehydrobromination of the 2-bromocycloalkanones (VII) is preferably carried out in dimethylformamide with a mixture of lithium bromide and lithium carbonate at the reflux temperature for a period of about 30 minutes to an hour or so. The so formed cycloalk-2-en-1-ones (VIII) are also isolated by standard procedures well known in the art. Substitution of X--(CH₂)_(m) --C(R₄)₂ --CH₂ --CO₂ C₂ H₅ for (II) in Flowsheet A and carrying through the sequence of transformations illustrated therein is productive of the following cycloalk-2-en-1-one (VIIIa): ##EQU5## wherein X, n, m and R₄ are as hereinabove defined.

The required cycloalk-2-en-1-one intermediates of general structure (XVI), wherein the side-chain has a lower alkyl group, fluorine atom or phenyl group alpha to the carbethoxy function, may be prepared in accordance with the following reaction scheme: ##SPC5##

wherein n, m and R₅ are as hereinabove defined and G is a lower alkyl or aryl group. In accordance with this reaction scheme, the 2-(ω-carbethoxyalkyl)cycloalk-2-en-1-ones (IX) are converted to the corresponding 1-methoximino-2-(ω-carbethoxyalkyl)-2-cycloalkenes (X) by treatment with methoxyamine. With the ring carbonyl function thus blocked it is possible to effect a preferential reduction of the ester group by treatment with diisobutylaluminum hydride. The resulting alcohol (XI) is converted to a tosylate derivative (XII), which undergoes displacement on treatment with the sodium salt of a diethyl R₅ -substituted malonate (XIII) to provide the disubstituted malonate derivatives (XIV). Hydrolysis and decarboxylation as well as concomittant cleavage of the methoximino blocking group provides the desired 2-(ω-carboxy-ω-R₅ -substituted-alkyl)cycloalk-2-en-1-ones (XV), which are readily converted to the corresponding ester (XVI) by the usual procedure via the acid chloride and subsequent treatment with the appropriate alcohol in the presence of a tertiary amine.

The requisite 2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-ones (XXII) and 2-(ω-carbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI) may be prepared in accordance with the reaction schemes of Flowsheet C, wherein n and m are as hereinbefore defined. ##SPC6##

In accordance with the reaction scheme shown in Flowsheet C, for the preparation of the oxa derivative (XXII), an appropriate 2-(ω-carbethoxyalkyl)cycloalk-2-en-1-one (XVII) is converted to the corresponding methoxime (XVIII), the ester function of which is then preferentially reduced with diisobutylaluminum hydride to afford the methoxime alcohol (XIX). The alcohol (XIX) is converted on treatment with n-butyl lithium to the lithio alcoholate, which then is O-alkylated by reaction with ethyl bromoacetate to provide (XX). Hydrolysis with acetone-aqueous hydrochloric acid furnishes the deblocked keto-acid (XXI), which is then re-esterified with ethanol in the presence of p-toluenesulfonic acid to give the required 2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-one (XXII). O-Alkylation can also be accomplished by treatment of the lithio alcoholate of (XIX) with sodium or other metal salt of bromoacetic acid, in which case the free carboxylic acid corresponding to ester (XX) is obtained. Hydrolysis as for (XX) provides the keto acid (XXI).

The preparation of the thia derivative (XXVI), proceeds from the intermediate alcohol (XIX), which after conversion to the tosylate intermediate (XXIII) and reaction with the sodium salt of ethyl mercaptoacetate furnishes intermediate (XXIV). Deblocking of XXIV with acetone-aqueous hydrochloric acid provides the keto-acid (XXV), which on re-esterification with ethanol gives the required 2-(ωcarbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI).

Certain of the 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives of this invention, as defined in the general formula on page 1 above, may be prepared from cycloalkenone (XXXI) and the triphenylmethoxy substituted 1-alkyne (XXVII) as depicted in Flowsheet D. In Flowsheet D, n, R₃, R'₃ and Z are as hereinabove defined; R'₂ is a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups each having from one to three carbon atoms, a straight chain alkenyl methyl group having from two to nine carbon atoms, or a straight chain alkenyl methyl group having from two to nine carbon atoms and substituted with one or two alkyl groups having between them 2 to 5 carbon atoms; and R is a lower alkyl group. ##EQU6##

In accordance with the reaction scheme of Flowsheet D, the triphenylmethoxy substituted 1-alkyne (XXVII) is treated with diisobutylaluminum hydride (XXVIII). This reaction of the 1-alkyne (XXVII) with diisobutylaluminum hydride (XXVIII) provides the alane (XXIX) containing the trans-double bond and is carried out in an inert solvent such as benzene, toluene, and the like at temperatures in the range of 40°-60°C. for several hours. It can also be carried out in a solvent such as tetrahydrofuran, usually in an approximate 2:1 mixture with benzene or hexane; in which case the reaction requires somewhat more vigorous conditions, usually treating at about 70°-75°C. for about eighteen hours. The subsequent reaction with methyl or n-butyl lithium (R-Li) is preferably carried out in a mixture of the above solvents with an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran and the like. This reaction is rapid and is preferably carried out at 0°-10°C. with cooling. The conjugate 1,4-addition of the resulting alanate salt (XXX) to the cycloalk-2-en-1-one (XXXI) is preferably carried out at ambient temperatures for a period of 12 to 24 hours. This reaction is also best carried out in an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran, and the like. The intermediate alanate-enolate adduct is then carefully hydrolyzed in situ with dilute hydrochloric acid with cooling, and the products (XXXII) are isolated in the usual manner well known in the art. Removal of the triphenylmethyl blocking group can then be accomplished by treating with weak acid. A preferred procedure involves heating at 45°C. for 3.5 hours in a solvent system consisting of acetic acid:tetrahydrofuran:water in the proportion of 4:2:1. Saponification in the usual manner of the resulting alkyl ester (XXXIII, R₃ =alkoxy) provides the corresponding carboxylic acid (XXXIII, R₃ =OH).

All available evidence leads us to the conclusion that in the product (XXXIII) the two side-chains attached to C₈ and C₁₂ are trans to each other. However, we are not certain of the configurational relationship in product (XXXII) as it is obtained directly from the alanate process. These products may have the side-chains in a trans or cis relationship or they may be a mixture containing both the trans- and cis-isomers. This is indicated in the nomenclature of the compounds involved by the designation of 8ξ. In order to ensure a trans-relationship in both (XXXII) and (XXXIII) these products can be submitted to conditions known in the literature to equilibrate the cis-8-iso-PGE₁ to a mixture containing about 90% of the trans product. These conditions involve treatment with potassium acetate in aqueous methanol for 96 hours at room temperature.

The triphenylmethyl blocking group for the hydroxy function in (XXVII) etc. is an important feature of this process and other oxygen blocking groups, e.g., tetrahydropyranyl and alkyl, are not compatible with a clean cis-addition of diisobutyl aluminum hydride (XXVIII) to the alkyne (XXVII) to provide the desired trans-vinyl function. Alternative procedures for the preparation of novel lithio alanate agents useful for the introduction of the Δ¹³ -trans 15-oxy β-chain by conjugate 1,4-addition are illustrated in Flowsheet K further below.

The intermediates for the introduction of the Δ¹³ -15-hydroxy side-chain are an integral part of this invention and they may be represented by the following general formulae (A), (B), (C), (D) and (E) wherein R'₂ is as hereinabove defined, R is a lower alkyl group, not necessarily the same for each use, and R' is an alkyl group having from one to ten carbon atoms not necessarily the same for each use, W₁ is lower alkoxy, triphenylmethyl, or a triphenylmethyl group in which one or two of the phenyl rings is substituted with a lower alkoxy group; W₂ is lower alkoxy, triphenylmethyl, a triphenylmethyl group in which one or two of the phenyl rings is substituted with a lower alkoxy group, tetrahydropyranyl, α-(lower alkoxy) substituted lower alkyl, t-butyl, or a tri-(lower alkyl)silyl group; X₁ is iodo or bromo; s is an integer having the value of one to three inclusive, and t is an integer having the value of one to three inclusive, with the proviso that the sum of s and t must be equal to four. ##EQU7##

The alanate conjugate addition procedure is also useful for the synthesis of prostaglandin E₁ (XL) as illustrated in Flowsheet E. This reaction sequence is carried out in the same manner as described for the sequence in Flowsheet D. It is to be noted that the introduction of the Δ¹³ -15-oxy chain proceeds trans to the 11-oxy function. For this synthesis, it is best to use the tetrahydropyranyl or trialkylsilyl esters, since these esters can be hydrolyzed under conditions compatible with the stability of the β-ketol feature of prostaglandin E₁. Alkyl esters would be hydrolyzed by fermentation with Baker's Yeast. The tetrahydropyranyl or trialkylsilyl, and triphenylmethoxy blocking groups are removed by mild acid treatment, for example with acetic acid:tetrahydrofuran:water (4:2:1) as described hereinabove. Application of the lithio alanate conjugate addition process to the synthesis of prostaglandins E₂ and E₃ is described below in connection with Flowsheet N. ##EQU8## ##SPC7##

The 13-dihydro derivatives (C₁₃ -C₁₄ is ethylene) of this invention can be prepared by reduction of the Δ¹³ function in the corresponding 13-prostenoic acids or esters. This reduction can be accomplished by hydrogenation. However this procedure is not cleanly applicable in the presence of other double bonds in the molecule. In the latter instance the 13-dihydro derivatives are preparable via conjugate addition of a Grignard derivative (XLII) to cycloalkenone (XLI) in the presence of a catalyst such as the tributylphosphine-cuprous iodide complex as set forth in Flowsheet F, wherein n Z, R₂ and R'₃ are as hereinabove defined; Q is a blocking group; and X is chlorine, bromine or iodine, preferably bromine or iodine. The blocking group (Q) for the hydroxyl function in (XLII) can be any group stable to the Grignard reagent and which can later be removed by chemical treatment (e.g., mild hydrolysis or catalytic hydrogenolysis in the absence of carbon to carbon double bonds elsewhere in the molecule) to which the remainder of the molecule is stable. Suitable blocking groups, therefore, may be, for example, benzyl, diphenylmethyl, triphenylmethyl, tetrahydropyranyl, or a moiety of the formula: ##EQU9## wherein R₁₁ is hydrogen, methyl or ethyl. Among the above-described blocking groups, we have found tert-butyl to be particularly convenient and useful. ##SPC8##

In accordance with the above reaction scheme, the conjugate 1,4-addition of a 3-(substituted hydroxy)alkyl or alkenyl magnesium halide (XLII) to a cycloalk-2-en-1-one (XLI) is carried out in the presence of a catalyst. In general, Grignard reactions with conjugated ketones provide 1,2-addition products; conjugate 1,4-addition is usually accomplished when the reaction is carried out in the presence of a cuprous chloride or cuprous acetate catalyst. It is therefore most unexpected that the reaction of the cycloalkenone (XLI) with a Grignard reagent (XLII) in the presence of either of the aforementioned catalysts does not give appreciable amounts of the desired 1,4-conjugate addition products. The novel feature of our process is provided by the use, as a catalyst, of a cuprous halide complex with a trisubstituted phosphine, a trialkyl phosphonate, a tertiary amine or a heterocycle containing a basic nitrogen (e.g., pyridine). We have found it preferable to use tributylphosphine-cuprous iodide complex; (C₄ H₉)₃ P.CuI. The reaction is best carried out in the usual way in an ether-type solvent such as diethyl ether, dibutyl ether, tetrahydrofuran, and the like, at room temperature for a period of time of from two to eighteen hours. The intermediate magnesium halide-enolate adduct is then hydrolyzed in situ, preferably with ammonium chloride, at room temperature and the product (XLIII) is isolated in the usual manner well known in the art.

When the blocking group is a tertiary alkyl moiety such as tert-butyl, deblocking of (XLIII) to afford (XLIV) is conveniently effected by treatment with glacial trifluoroacetic acid at from -5°C. to 10°C. for a period of one to three hours. Since this procedure may lead to partial trifluoroacetylation of the free hydroxy function, it is preferably followed by treatment with aqueous ammonia (about 1.0N concentration) for about 15 minutes at ambient temperatures. When the blocking group is tetrahydropyranyl, its removal is readily effected with dilute acid. When the blocking group is a moiety such as benzyl, diphenylmethyl or triphenylmethyl, deblocking of (XLIII) is conveniently effected by catalytic hydrogenolysis, procedures for which are well known in the art. In the instance of triphenylmethyl, deblocking is preferably effected by treating with acetic acid:tetrahydrofuran:water (4:2:1) at about 45°C. for about 3.5 hours.

Mild acid treatment results in hydrolysis of the tetrahydropyranyl esters; alkyl esters can be hydrolyzed by the usual saponification techniques.

When the cycloalkanone esters (XLIII) are formed by quenching of the reaction mixture with aqueous ammonium chloride solution, the relative stereochemical relationship of the two side-chains is not known with certainty. Therefore, the bond linking the Grignard-derived side-chain to the cycloalkyl ring is indicated by a ˜ bond in (XLIII). However, in any case, the subsequent deblocking and ester hydrolysis procedures ensure the development, at least in predominant proportion, of the thermodynamically favored trans-relationship between the two side-chains, as is depicted in structure (XLIV) of the reaction scheme.

An alternative method for the introduction of the Δ¹³ -15-hydroxy side-chain involves 1,4-conjugate addition to cycyloalkenone (LV) of a vinyl Grignard reagent [(LIII) + (LIV)] in the presence of a catalyst such as the tributylphosphine cuprous iodide complex followed by deblocking. From this process, in addition to the product (LVIII) containing the C₁₃ -C₁₄ moiety as a trans-vinylene function there also is obtained the corrresponding product (LIX) in which the C₁₃ -C₁₄ moiety is a cis-vinylene function. These novel cis-Δ¹³ derivatives are also embraced within the scope of this invention. The reaction sequence for the "vinyl" Grignard process is illustrated in flowsheet G, which follows, and in which W₂, n, Z, R₃ and R'₃ are as hereinabove defined, and R"₂ is a straight chain alkyl group having from 2 to 10 carbon atoms, or a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups having from one to three carbon atoms. ##EQU10##

In accord with the reaction sequence of Flowsheet G the vinyl Grignard reagent (LIII + LIV), is prepared under an inert atmosphere in a relatively limited amount of anhydrous tetrahydrofuran. More vigorous conditions (e.g., heating in an oil bath at 70°-80°C., one hour), for the formation of the Grignard reagent (LIII + LIV) favors the proportion of Δ¹³ -cis isomer (LIX) in the product of conjugate addition. Milder conditions (for example 35°-47°C., one hour) favors the proportion of Δ¹³ -trans isomer (LVIII) in the final product.

Conjugate addition of the vinyl Grignard reagent mixture [(LIII) + (LIV)] to cycloalkenone (LV) is then preferably carried out by addition of the Grignard to the cycloalkenone dissolved in an ether type solvent, e.g., diethylether, containing a catalyst such as the tributylphosphine-cuprous iodide complex at a temperature of about 0°C. After a period of about 30 minutes to 3 hours the reaction mixture is poured onto aqueous concentrated ammonium chloride solution to give (LVI) + (LVII). As explained hereinabove, at this stage the relationship of the two side-chains to each other is not determined. In any event, deblocking the 15-hydroxy function with weak acid (which procedure also hydrolyzes trialkylsilyl or tetrahydropyranyl esters) provides the product (LVIII) and (LIX) in which the chains are trans to each other. In the instance of alkyl esters, saponification provides the corresponding carboxylic acids. The Δ¹³ -cis and Δ¹³ -trans-isomers can be separated from each other by the usual techniques of chromatography; particularly useful is liquidliquid partition chromatography.

The precursor 3-hydroxy-1-trans-alkenyl bromides (LI) can be prepared, as illustrated in Flowsheet G, by condensation of acetylene (XLV) with an acid chloride (XLVI) in the presence of aluminium trichloride. The resulting 3-oxo-1-chloro-trans-1-alkylene (XLVII) is then converted to the corresponding 1-bromo derivative (XLVIII), by reaction with excess lithium bromide. This reaction is preferably carried out in ketone solvents, such as 2-pentanone or acetone. Reduction of the 3-keto function in (XLVIII), with for example, sodium borohydride provides the alcohol (LI). The alcohol function is then blocked to give (LII). Alternatively, the 3-oxo vinyl bromide (XLVIII) can be prepared directly from the acyl bromide (L) and acetylene (XLIX) in the presence of aluminum tribromide, preferably in ethylene dibromide.

The "vinyl Grignard" procedure outlined in Flowsheet G represents a novel, useful and convenient procedure for the synthesis of 13-prostenoic acids and the novel Grignard reagents represented by formulae (LIII) and (LIV) are to be considered as embraced within the scope of this invention.

The "vinyl Grignard" technique can also be applied to a useful synthesis of prostaglandin E₁ and the novel Δ¹³ -cis-prostaglandin-E₁ as illustrated in Flowsheet H, below. Thus, treatment of cyclopentenone (LX) with Grignard [(LXI + (LXII)] in accordance with the considerations discussed hereinabove, provides the conjugate addition products (LXIII) plus (LXIV), mild acid hydrolysis of which furnishes prostaglandin E₁ (LXV) and Δ¹³ -cis prostaglandin E₁ (LXVI), separable by chromatography. ##SPC9##

The preparation of the cycloalkenone intermediates (LXXVI, LXXVII) bearing a cis double bond in the carboxylic acid side chain can be accomplished by the sequence illustrated in Flowsheet I, which follows and in which n and p are as hereinabove defined. ##SPC10##

In the above Flowsheet I, the sequence wherein a 2-carbalkoxycycloalkanone (LXVII) is transformed to a 2-(β-hydroxyethyl)cycloalk-2-en-1-one (LXXIII) is carried out in the manner described in Flowsheet A. Methyl ether cleavage of the corresponding 2-(β-methoxymethyl)cycloalkenone is achieved by treating with boron tribromide. Oxidation of the alcohol (LXXIII) with Collins reagent [chromium trioxide-pyridine complex in methylene chloride under anhydrous conditions; J. C. Collins, W. W. Hess, and F. J. Frank, Tetrahedron Letters, 3363 (1968)] provides the aldehyde (LXXIV), which is then treated in anhydrous dimethylsulfoxide with the yield (LXXV) prepared from an (ω-carboxyalkyl)triphenyl phosphonium bromide and sodium hydride. The use of dimethylsulfoxide as a solvent for this reaction leads to the predominant formation of the desired cis double bond derivative (LXXVI). The acid function in (LXXVI) can be esterified in the usual fashion; with diazomethane, the methyl ester (LXXVII) is obtained.

Cyclopentenones such as (LXXVI wherein n=1) may also be prepared by the sequence illustrated in Flowsheet J, which follows and in which p is as hereinabove defined. ##EQU11##

In Flowsheet J above the bicyclic hemiacetal (LXXVIII) [P.A. Grieco, Journ. Org. Chem., 37, 2363 (1972)] is treated with ylid (LXXIX) to give the 1-hydroxy-3-cyclopentene (LXXX). Oxidation with Jones reagent gives the corresponding ketone (LXXXI), which on base treatment furnishes the required cyclopentenone (LXXII), which can then be esterified in the usual manner.

Certain of the intermediates illustrated in Flowsheets I and J, in particular the compounds of formulae (LXXI), (LXXII), (LXXIII), (LXXIV), (LXXVI) (LXXVII) (and related esters), (LXXX) and (LXXXI) are novel and useful compounds and are embraced within the scope of this invention.

Alternative procedures for the preparation of the alanate intermediates to that discussed in connection with Flowsheet D above are illustrated below in Flowsheet K, wherein R', R'₂, R"₂ and W₂ are as hereinabove defined. ##EQU12##

In accordance with the sequence of Flowsheet K above the 1-iodo-trans-1-alkenyl-3-oxo derivative (LXXXIV) is prepared by iodide interchange, preferably in acetone or similar ketone, from the corresponding chloride (LXXXIII), the preparation of which is described in connection with Flowsheet G above. Reduction of (LXXXIV) to the alcohol (LXXXVI) can be accomplished in the usual manner with sodium borohydride. The hydroxy function is then blocked to give (LXXXV, R'₂ -R"₂). Treatment of the acetylene, ##EQU13## with one equivalent of disiamylborane (prepared in situ from diborane and 2-methyl-2-butene) and then with excess anhydrous trimethylamine oxide followed by treatment with an aqueous solution of excess sodium hydroxide and a tetrahydrofuran solution of excess iodine is also productive of (LXXXV). Treatment of the trans-1-alkenyl iodide (LXXXV) at low temperatures, preferably at about -30°C. to -78°C., in an inert solvent, e.g., hexane or toluene, with an alkyl lithium, e.g., butyl lithium, provides the trans-1-alkenyl lithium reagent (LXXXVII). Treatment of this lithio derivative with tri-alkyl aluminum furnishes the trans-1-alkenyl trialkyl alanate (LXXXVIII). Treatment of a dialkyl aluminum chloride with two molar equivalents of lithio reagent (LXXXVII) gives the bis(trans-1-alkenyl)dialkyl alanate (LXXXIX) and treatment of an alkylaluminum dichloride with three molar equivalents of lithio reagent (LXXXVII) affords the tris(trans-1-alkenyl)alkyl alanate (XC).

Each of the three types of alanates, (LXXXVIII), (LXXXIX) and (XC), can be utilized for 1,4-conjugate addition reactions as described hereinabove in connection with Flowsheets D and E above. Thus, substitution of (LXXXVIII), (LXXXIX) or (XC) for alanate (XXX) in Flowsheet D will provide the indicated products of the Flowsheet. Similarly, substitution of (LXXXVIII), (LXXXIX) or (XC) in which R'₂ is n-pentyl for alanate (XXXVII) in Flowsheet E provides prostaglandins E₁. In general the mono alkenyl alanate (LXXXVIII) is preferred because it is more economical in the use of vinyl halide.

With regard to the cycloalkenones of Flowsheets D, E, F, G and H it should be noted that the blocking groups for the 4-hydroxy function as well as for the carboxylic acid may also be a tri-alkylsilyl group, e.g., trimethylsilyl, dimethyl-t-butylsilyl or dimethylisopropylsilyl. Cyclopentenones blocked in this manner are illustrated below in formula (XCI) and (XCII) wherein m, n, Z and R' (not necessarily the same for each use) are as hereinabove defined. ##EQU14##

All the novel products of this invention exclusive of certain intermediates bear a hydroxy or oxy function substituted at or at what ultimately becomes the C₁₅ atom of the product prostanoic acids and esters. Thus in at least most instances a 15-"normal" and a 15-"epi" racemate is obtained in at least near equal proportions. Each of the racemates contains equal amounts of the enantiomer wherein C₁₅ is in the S configuration and the enantiomer wherein it is in the R configuration. The racemates are separable from each other by the usual techniques of chromatography. Also, resolution in the usual way of the β-chain precursor [for example, the resolution of 3-hydroxy-1-octyne is described in the literature see R. Pappo, P. Collins and C. Jung. Ann. N.Y. Acad. of Science, 180 (Prostaglandins), 64(1971); J. Fried et al., ibid, p. 381.] Resolution prior to the conjugate addition operation will provide the diastereomers wherein the C₁₅ atom is either in the 15(S) or 15(R) configuration, as desired. Separation of the diastereomers so obtained, for example, by chromatography, will give the fully resolved (d and 1) products provided there are no asymmetric carbon atoms other than at C₈ and C₁₂. The presence of other asymmetric sites requires additional resolution steps in order to obtain a single atipode. The compounds of this invention embrace all possible optical isomers.

The 11-deoxy-9-keto derivatives (XCIV) of this invention can be converted to the corresponding 9-hydroxy derivatives. If this conversion is effected with sodium borohydride, the product is a mixture of 9α- and 9β-hydroxy derivatives (XCIII) and (XCV) as set forth in the following reaction scheme: ##SPC11##

wherein R₂, R₃, R₆, R₇, Z, n and -C₁₃ -C₁₄ - are as hereinabove defined. In general, when the reaction is carried out with lithium perhydro-9b-borophenalyl hydride [H. C. Brown and W. C. Dickason, Journ. Amer. Chem. Soc., 92, 709 (1970)] the product is at least predominantly the 9α-hydroxy derivative (XCIII), wherein the 9-hydroxy group is cis to the side-chain attached to C₈.

In accordance with accepted convention, an α-substituent at the 8-, 9-, or 12-positions is behind the plane of the paper whereas a β-substituent at these positions is in front of the plane of the paper. This is usually represented by a --- bond for an α-substituent, a -- bond for a β-substituent, and a bond where both are indicated. Thus, the 9-hydroxy derivatives may be variously represented as follows: ##EQU15##

A useful procedure for the introduction of the 15-lower alkyl group (R₆) is illustrated by the sequences of Flowsheet M, which follows. ##SPC12##

In Flowsheet M above n, Z, R₂, R₇ and R₆ are as hereinabove defined. In the sequence depicted in Flowsheet M the 9,15-diol (XCVI) is treated with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (XCVII), which preferentially oxidizes the allylic alcohol function at C₁₅ to give the 15-ketone (XCVIII). Blocking of the remaining hydroxy function as a trimethylsilyl ether gives (IC) which is reacted with the alkyl Grignard, R₆ MgI, to give the 15-alkyl-15-hydroxy derivative (CI). Hydrolysis of the silyl ether blocking group then gives the diol ester (C), saponification of which gives (CII). Oxidation of the secondary 9-hydroxy function in (C) provides the 15-alkyl-9-oxo ester (CIII), saponification of which furnishes (CIV). (A similar sequence can be effected with the Δ¹³ -cis-series.)

The processes of this invention are also useful for the preparation of prostaglandin E₂ and prostaglandin E₃ and thus also PGF₂.sub.α and PGF₃.sub.α by reduction, for example with lithium perhydro-9b-boraphenalyl hydride. The 4-hydroxycyclopentenone intermediate (CXI) required for these syntheses is prepared in accordance with the procedure illustrated in Flowsheet N which follows and in which is also shown the transformation of this compound to prostaglandins E₂ and E₃. In Flowsheet N, J is an appropriate blocking group for the hydroxy and ester function in (CXI) which is compatible with the conjugate addition reaction and also is ultimately removable by acid-catalyzed hydrolysis or other techniques which will not disrupt the sensitive 11-oxy-9-keto system in the products (CXIII), (CXV), (CXVIII) and (CXVII). Particularly useful for this purpose are the tetrahydropyranyl group and various trialkylsilyl groups (e.g., dimethylisopropylsilyl, trimethylsilyl, dimethyl-t-butylsilyl and the like. ##SPC13##

In accordance with the above reaction scheme the 3,4-epoxylactol (CV) [E. J. Corey and R. Noyori, Tetrahedron Letters, 311 (1970)] is treated with the ylide (CVI) to give the 3,4-epoxycyclopentanol (CVII) bearing the α-chain of the prostaglandin 2 series. Oxidation (for example with H₂ CrO₄.-H₂ SO₄ -ether or Jones reagent) of (CVII) provides the epoxy ketone (CVIII), mild base treatment of which results in the initial formation of the 4-hydroxycyclopent-2-en-1-one (CXI) and the isomeric 3-hydroxycyclopent-4-en-1-one (CX) as a mixture. Further treatment of this mixture with dilute base under mild conditions (preferably pH 10.3-10.6 for 24 hours) results in the isomerization of the 3-hydroxy isomer (CX) to the desired (CXI). We believe that the transformation of the epoxy ketone (CVIII) to the hydroxycyclopentenones (CX) and (CXI) and the isomerization of (CX) to (CXI) may take place through the intermediacy of the 3,4-diol (CIX). It is also conceivable that isomerization of (CX) to (CXI) procedes via the epoxy derivative (CVIII) or the corresponding α-epoxide (CXIb); it is further conceivable that (CVIII) procedes to (CX) and (CXI) directly without the intermediacy of (CIX). Another possible intermediate for the isomerization of (CX) to (CXI) is the corresponding diene (CXIa). The preparation of (CXI) is also possible via the α-epoxide series from (CXIc) via the α-epoxide corresponding to (CVII) and (CVIII) such as (CXIb) or via a mixture of the α and β epoxides. In practice, it is most convenient to utilize a mixture of α- and β-epoxides (CXIc and CV). The hydroxy and acid function in the 4-hydroxycyclopentenones (CXI) are then appropriately blocked to give (CXII). Appropriate blocking groups are tetrahydropyranyl, trimethylsilyl, dimethyl-isopropylsilyl, dimethyl-t-butylsilyl and the like. Treatment of (CXII) with the lithio alanate (CXIV) or its equivalent (see the discussion hereinabove for Flowsheets K and E) gives the conjugate addition product (CXIII) in which the configuration at C₈ is undetermined. Mild acid treatment, for example with acetic acid:tetrahydrofuran:water,(4:2:1), of (CXIII) results in the removal of blocking groups, and if necessary equilibration to the alltrans configuration, to give prostaglandin E₂ (CXV). Similarly treatment of (CXII) with the lithio alanate (CXVI) gives prostaglandin E₃ (CXVII).

Substitution in Flowsheet N, of ylide (CXIX), wherein p is as hereinabove defined, for the ylide (CVI) provides, by transformations analogous to those described in Flowsheet N [(CV) to (CXI) and (CXII)], the 4-hydroxycyclopent-2-en-1-ones (CXX) and their blocked ether-esters (CXXI). These novel and useful intermediates are a part of the present invention. ##SPC14##

The 8β-lower alkyl group (R'₇) is introduced as illustrated in Flowsheet O below via the bromomagnesium enolate (CXXV). This novel and useful intermediate is obtained by conjugate addition of the 1-alkenyl Grignard reagent [(CXXIII) + (CXXIV)], preferably prepared at about 35°C., to the cycloalkenone (CXXII) in the presence of a catalyst such as the tri-n-butylphosphine cuprous iodide complex as described hereinabove in connection with Flowsheets G and H. It is also possible to utilize for these purposes in an analogous manner the magnesio enolate (CXXVIII) obtained by conjugate addition of Grignard (XLII) to cycloalkenone (XLI) as described hereinabove in connection with Flowsheet F, in which case the 13,14-dihydro derivative of this invention are obtained. In Flowsheet O below, n, Z, R₃, R'₃, R'₂, W₂, R₂, Q and X are as hereinabove defined and R'₇ is an alkyl group having up to 3 carbon atoms. When the magnesio enolate (CXXV) is treated with a lower alkyl halide, e.g., methyl iodide, it undergoes alkylation at the 8β-site providing, after deblocking of the 15-oxy group in intermediate (CXXVI), the 8β-alkyl derivative (CXXVII). In the instance of alkyl esters, saponification gives the corresponding carboxylic acids (CXXVII, R₃ =OH). The compounds corresponding to (CXXVII) wherein C₁₃ -C₁₄ is a cis-vinylene double bond are preferably prepared by utilizing the vinyl Grignard reagent prepared at temperatures in the range of 70°-75°C., as discussed hereinabove (Flowsheets G and H).

Also obtained from the alkylation of (CXXV) is the 8α-alkyl-8-iso derivative corresponding to (CXXVI), which after deblocking provides the 8α-alkyl-8-iso-products (CXXIX). Usually the 8α-product is formed to a significantly lesser extent than the 8β-product (CXXVI). The 8α and 8β products are separable from each other by the usual techniques of chromatography. ##SPC15##

Application of the 8-alkylation process to the 11-oxy series provides the novel compounds of formula (CXXX), wherein R₁, R₂, R₆, Y and C₁₃ -C₁₄ are as hereinabove defined and wherein R'₇ is an alkyl group having up to 3 carbon atoms, R₈ is selected from the group consisting of hydrogen, lower alkanoyl, tetrahydropyranyl and tri-lower alkylsilyl groups, R₉ is selected from the group consisting of hydroxy, alkoxy having from 1 to 12 carbon atoms, tetrahydropyranyloxy and tri-lower alkyl silyloxy groups, Z₂ is a divalent radical selected from the group consisting of those of the formulae: ##EQU16## wherein m, p, R₄ and R₅ are as hereinabove defined; and the moiety ##EQU17## when Y is ##EQU18## can also be the divalent radical ##EQU19## with the proviso that only one unsaturated bond can be directly adjacent to C₁₅ ; and with the second proviso that when R₆ is alkyl then R₁ is hydrogen; and with the third proviso that the groups attached to C₈ may be in the 8β-alkyl (8-iso) configuration: ##EQU20## ##SPC16##

The novel compounds of formula (CXXX) are also embraced by this invention. The preparation of these compounds may be illustrated by the reaction sequence of Flowsheet P below, wherein R₉, Z₂, W₂, R"₂, R'₇ and R₃ are as hereinabove defined and R'₈ has all the possibilities defined above for R₈ except that it is not hydrogen. ##SPC17##

In accordance with the sequence of Flowsheet P above, treatment of the ether-ester 4-oxycyclopentenone (CXXXI) with the 1-alkylene Grignard reagents [(CXXIII) + (CXXIV)] (see Flowsheet O) gives the bromomagnesio enolate (CXXXII). This operation also results in the introduction of the trans C₁₃ -C₁₄ double bond (as shown in CXXXII), as well as the corresponding compound with the cis-double bond. The trans bond is favored when the Grignard is prepared at lower temperatures, about 35°C.; the cis-bond at higher temperatures, about 70°-75°C. This point is more fully discussed above in connection with Flowsheets G and H. The magnesio elonate (CXXXII) is a key intermediate and when it is treated with a lower alkyl halide, e.g. methyliodide, it undergoes alkylation to give the 8β-lower alkyl derivative (CXXXIII). Deblocking of the 15-hydroxy blocking group (e.g., triphenylmethyl), and of the 11-hydroxy tetrahydropyranyl or trialkylsilyl ether blocking groups as well as of the tetrahydropyranyl or trialkyl silyl esters is accomplished under mild acid conditions, e.g. heating at 45°C. for 3.5 hours in a solvent system consisting of acetic acid:tetrahydrofuran:water (4:2:1). This procedure provides (CXXXV). The compounds of structure (CXXXV) or (CXXXIII) can be converted to 8β-alkyl prostaglandins of the A class (CXXXIV) by treatment with acid or base, a preferred procedure involves treatment in tetrahydrofuran:water (2:1) solvent 0.5N in hydrochloric acid for about 70 hours at ambient temperatures.

The novel compounds of this invention represented by formula (CXXXIV) and related compounds are particularly interesting sunce they represent "stabilized" prostaglandin A types, which cannot rearrange to the biologically relatively inactive prostaglandins of the B series.

Utilization of Grignard (XLII) (see Flowsheet F, hereinabove) in the sequence of Flowsheet P provides the compounds of (CXXX) wherein C₁₃ -C₁₄ is ethylene. Provided there are no other double bonds in the molecule these substances can also be obtained by catalytic hydrogenation of the compounds represented by formula (CXXXV).

The alkylation process described above for Flowsheets O and P also gives the corresponding 8α-alkyl derivatives which are separable from the 8β-alkyl isomer by chromatography. Thus, for example, in Flowsheet O treatment of enolate (CXXV) with R'₇ I gives not only the 8β-alkyl product (CXXVI) as shown, but there also is obtained the 8α-alkyl derivative (CXXXVI) shown below. In Flowsheet P, alkylation of enolate (CXXXII) also provides, in addition to (CXXXIII) shown, the 8α-alkyl-8-iso product (CXXXVII), shown below. These 8α-alkyl-8-iso derivatives can be deblocked and carried through the same series of transformation shown for the 8β-derivatives (CXXVI) and (CXXXIII) in Flowsheets O and P, respectively. These novel 8α-alkyl-8-iso derivatives and their transformation products are also a part of this invention, as are the key intermediate enolates represented by structures (CXXV) and (CXXXII). ##SPC18##

The novel compounds of the present invention have potential utility as hypotensive agents, anti-ulcer agents, agents for the treatment of gastric hypersecretion and gastric erosion, bronchodilators, antimicrobial agents, anticonvulsants, abortifacients, agents for the induction of labor, agents for the induction of menses, fertility-controlling agents, central nervous system regulatory agents, analgesic agents, salt and water-rentention regulatory agents, diuretics, fat metabolic regulatory agents, serum-cholesterol lowering agents, anti-inflammatory agents and as agents for the inhibition of platelet aggregation, and for the treatment of periodontal disease, glaucoma, uveitis, sickle cell anemia and psoriasis. Certain of the novel compounds of this invention possess utility as intermediates for the preparation of other of the novel compounds of this invention.

The compounds of this invention provide protection against the ulcerogenic properties of indomethacin. This assay was carried out in the following manner.

Rats were starved for 48 hours (water was given ad libitum). Indomethacin (20 mg./kg. of body weight) was administered by the subutaneous route and one-half the dose of the test compound was administered by gavage at the same time. After three hours, the second half of the test compound was administered also by Gavage. Five hours after the administration of indomethacin the animals were decapitated and the stomachs removed. The stomachs were washed with distilled water, blotted on gauze, cut along the larger curvature, and the contents rinsed with distilled water. The stomachs were spread out, pinned on a cork and visualized under magnifying glass for ulcers. The criteria for scoring of ulcers was as previously reported. [Abdel-Galil et al. Brit. J. Pharmac. Chemotherapy 33:1-14 (1968)].

Score

0 - Normal stomach

1 -Petechial hemorrhage or pin point ulcer

2 - 1 or 2 small ulcers

3 - Many ulcers, a few large

4 - Many ulcers, mainly large

Control animals treated with indomethacin but not test compound consistently give scores of about 3.0-3.5. Control animals treated with neither indomethacin nor test compound give scores of about 0.5-0.8. The results obtained in this assay with typical compounds of the present invention are set forth in Table 1 below. Compounds producing a score of 2.5 or lower are considered to be active.

                  TABLE I                                                          ______________________________________                                                      Total Oral                                                                     dose; mg./kg.                                                                            Score                                                                of body                                                           Compound       weight      Treated  Control                                    ______________________________________                                         9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoic acid                                            25          1.7      3.2                                        9-oxo-15-hydroxy-13-cis-prostenoic acid                                                       100         1.3      3.0                                        9-oxo-15-hydroxy-2-ethyl-13-trans-prostenoic acid                                             50          2.2      3.0                                        9-oxo-8β-methyl-15-hydroxy-13-trans-prostenoic acid                                      12.5        2.0      3.0                                        9-oxo-3-thia-15-hydroxy-13-trans-prostenoic acid                                              25          1.8      3.2                                        9-oxo-3-thia-15-epi-hydroxy-13-trans-prostenoic acid                                          25          2.3      3.2                                        ______________________________________                                    

The novel compounds of the present invention are also effective inhibitors of gastric acid secretion and of ulcer development in experimental animals, and thus are potentially valuable as agents for the control of gastric acid secretion and of gastric erosion and as anti-ulcer agents. Gastric acid secretion inhibitory action is usually measured by the "Shay rat" procedure .sup.(1,2) with some modifications as follows.

The rats (male, CFE strain) were starved for 48 hours (water was given ad libitum) to permit evacuation of stomach contents. On the morning of the experiment, under ether anesthesia, the abdominal region was shaved and a midline incision (1-11/2inches) was made with a scapel. With the help of a closed curved hemostate the duodenum was picked up. Upon getting the duodenum into view, fingers were used to pull the stomach through the opening, the stomach was then gently manipulated with fingers to rid the stomach of air and residual matter which were pushed through the pylorus. Two-5 inch sutures were drawn under the pyloric-duodenal puncture. A ligature, at the juncture was formed with one of the threads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./mg. body weight, were injected into the duodenum as close as possible to the first ligature. After injection the second ligature was tightened below the injection site to minimize leakage. The stomach was placed back through the opening into the abdominal cavity, the area of incision was washed with saline and the incision was closed with autoclips. (Occasionally, instead of an intraduodenal injection, animals were dosed by the oral or subcutaneous route. In the latter case, dosing was done 30 to 60 minutes before the operation.)

Three hours later, the rats were decapitated and exanguinated, taking care that blood did not drain into the estophagus. The abdominal cavity was exposed by cutting with scissors and the esophagus close to the stomach was clamped off with a hemostat, the stomach was removed by cutting above the hemostat (the esophagus was cut) and between the two sutures. Extraneous tissue was removed, the stomach washed with saline and blotted on gauze. A slit was carefully made in the stomach which was held over a funnel and the contents were collected in a centrifuge tube. The stomach was further cut along the outside edge and turned inside out. Two ml. H₂ O were used to wash the stomach contents into the respective centrifuged tube. The combined stomach contents and wash were then centrifuged out for 10 minutes in the International Size 2 Centrifuge (setting at 30). The supernatant was collected, volume measured and recorded, 2 drops of a phenolphthalein indicator (1 in 95% ethanol) were added and the solution was titrated with 0.02N NaOH (or with 0.04N NaOH when large volumes of stomach contents were encountered) to pH 8.4 (because of usual coloring of the stomach contents, phenolphthalein was only used to permit visual indication that the end point was near) and the amount of acid present was calculated.

Compounds inducing inhibition of gastric acid secretion of 20% or more were considered active. In a representative operation, and merely by way of illustration, the results obtained with this assay with a typical compound of the present invention are given in Table 2, below.

                  TABLE 2                                                          ______________________________________                                                        Intraduodenal                                                                  dose, mg./kg. Percent                                           Compound       of body weight                                                                               Inhibition                                        ______________________________________                                         9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acid                                        100           51                                                ______________________________________                                    

Bronchodilator activity was determined in guinea pigs against bronchospasms elicited by intravenous injections of 5-hydroxytryptamine, histamine or acetylcholine by the Konzett procedure. [See J. Lulling, P. Lievens, F. El Sayed and J. Prignot, Arzeimittel-Forschung, 18 995 (1968).]

In the Table which follows bronchodilator activity for representative compounds of this invention against one or more of the three spasmogenic agents is expressed as an ED₅₀ determined from the results obtained with three logarithemic cumulative intravenous doses.

                  TABLE 2A                                                         ______________________________________                                         Bronchodilator Activity (Konzett Assays)                                       ED.sub.50, mg./kg.                                                                       Spasmogenic Agent                                                                5-hydroxy-                                                         Compound    tryptamine histamine  choline                                      ______________________________________                                         9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoic acid                                          --        81.3×10.sup.-.sup.6                                                                 --                                           9-oxo-15-hydroxy-13-cis-prostenoic acid                                                    106×10.sup.-.sup.6                                                                  81.3×10.sup.-.sup.6                                                                 320×10.sup.-.sup.6                     9-oxo-15-hydroxy-2-ethyl-13-trans-prostenoic acid                                          329×10.sup.-.sup.6                                                                   145×10.sup.-.sup.6                                                                 533×10.sup.-.sup.6                     9-oxo-15-hydroxy-16-prostynoic acid                                                        50.8×10.sup.-.sup.6                                                                 92.6×10.sup.-.sup.6                                                                 320×10.sup.-.sup.6                     ______________________________________                                    

The novel compounds of the present invention are useful as hypotensive agents and their prostaglandin-like hypotensive activity was demonstrated in the following test procedure. This procedure is a modification of the technique described by Pike et al., Prostaglandins, Nobel Symposium 2, Stockholm, June, 1966; p. 165.

Male Wistar strain rats (Royal Hart Farms) averaging approximately 250 grams in weight were fastened to rat boards in a supine position by means of canvas vests and limb ties. The femoral area was infiltrated subcutaneously with lidocaine and the iliac artery and vein were exposed and cannulated. Arterial blood pressure (systolic/diastolic) was recorded using a Statham P₂₃ Db pressure, the animals were anethetized before use with pentobarbital, 30 mg./kg. of body weight intravenously, and also were given hexamethoxium bitartrate, 2 mg./kg. of body weight intravenously. The test compounds were prepared by ultrasonic dispersion in a saline-Tween 80 vehicle. A constant intravenous dose volume of 0.5 ml. was administered and test doses ranged from 0.1 to 10.0 mg./kg. of body weight. Increasing or decreasing doses were selected depending on the dose response obtained. In Table 2B below are set forth the minimal doses required to produce a decrease of about 10 mm. in diastolic blood pressure for typical compounds of the present invention.

                  TABLE 2B                                                         ______________________________________                                         HYPOTENSIVE ACTIVITY                                                                            Minimal effective                                                              hypotensive dose                                              Compound         (mg./kg. of body wt.)                                         ______________________________________                                         2-ethyl-9-oxo-15-hydroxy-13-trans-prostenoic acid                                               <2                                                            2-ethyl-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid                                           2-4                                                           2-ethyl-9-oxo-15-hydroxy-prostanoic acid                                                        0.2                                                           2-methyl-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid                                          2                                                             2-methyl-9-oxo-15-hydroxy-13-trans-prostenoic acid                                              2                                                             8β-methyl-9-oxo-15-hydroxy-13-trans-prostenoic acid                                        2                                                             9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoic acid                                              <8                                                            3,3-dimethyl-9-oxo-15-hydroxy-13-trans-prostenoic acid                                          8                                                             9-oxo-15-hydroxy-13-cis-prostenoic acid                                                         2-4                                                           9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid                                             <2                                                            9-oxo-15-hydroxy-16-prostynoic acid                                                             2                                                             9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostatrienoic acid                                      <2                                                            3-oxa-9-oxo-15-hydroxy-13-trans-prostenoic acid                                                 <2                                                            3-oxa-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid                                             1-2                                                           3-thia-9-oxo-15-hydroxy-13-trans-prostenoic acid                                                2                                                             3-thia-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid                                            2                                                             9-oxo-15-hydroxy-16-trans-prostenoic acid                                                       <2                                                            2-phenyl-9-oxo-15-hydroxy-13-trans-prostenoic acid                                              8                                                             2-phenyl-9-oxo-15-epi-hydroxy-13-trans-prostenoic acid                                          2-8                                                           2-fluoro-9-oxo-15-hydroxy-13-trans-prostenoic acid                                              8                                                             7a,7b-bishomo-9-oxo-15-hydroxy-13-trans-prostenoic acid                                         <8                                                            9-oxo-10a-homo-15-hydroxy-13-trans-prostenoic acid                                              2                                                             9-oxo-10a-homo-15-epi-hydroxy-13-trans-prostenoic acid                                          2                                                             9-oxo-15-hydroxy-15-methyl-5-cis,13-trans,17-cis-prostatrienoic                                 <2id                                                          Ethyl 3-oxa-9-oxo-15-hydroxy-13-trans-prostenoate                                               0.2                                                           Ethyl-3-oxa-9-oxo-15-epi-hydroxy-13-trans-prostenoate                                           0.2                                                           Ethyl 9-oxo-10a-homo-15-hydroxy-13-trans-prostenoate                                            2                                                             9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic acid                                        <2                                                            9-oxo-15-hydroxy-17,17-dimethyl-13-trans-prostenoic acid                                        2                                                             3-thia-9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic                                      <2id                                                          3-oxa-9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic                                       <2id                                                          ______________________________________                                    

This invention will be described in greater detail in conjunction with the following specific examples. In these examples it is to be noted that Example 724 follows directly after Example 699.

In the examples which follow reference to 15-hydroxy or 15-oxy derivatives, unless otherwise indicated is inclusive of both the 15-epi and 15-normal racemates. In addition, all possible antipodes resulting from asymetry at C₈, C₁₂ and elsewhere in the prostenoic acid molecule are included.

EXAMPLE 1 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(4-carbethoxybutyl)cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolate in dimethoxyethane, prepared from 187 g. (1.248 moles) of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g. (1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 l. of dimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl 5-iodovalerate. The reaction mixture is stirred and heated at reflux for 18 hours. The mixture is cooled and filtered. The solvent is removed from the filtrate by evaporation and the residue is poured into dilute hydrochloric acid and extracted with ether. The combined extracts are washed with water and saline, dried over magnesium sulfate and evaporated to give an oil. The oil is distilled under reduced pressure to give 274 g. of a light yellow oil, b.p. 140°-143°C. (0.17 mm).

EXAMPLE 2 Preparation of 2-(4-carboxybutyl)cyclopentan-1-one

A stirred mixture of 274 g. of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of 20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux for 20 hours. Solution occurs in approximately 1/2 hour. The solution is cooled and diluted with water and extracted with ether. The combined extracts are washed with saline and dried over magnesium sulfate and evaporated. The residue is evaporated twice with toluene to give 144 g. of an oil.

EXAMPLE 3 Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mole) of 2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and 1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The ether solution is washed with saline, dilute sodium bicarbonate solution and again with saline, dried over magnesium sulfate and evaporated. The oil is distilled under reduced pressure to give 149 g. of a colorless oil, b.p. 106°-109°C. (0.23 mm).

EXAMPLE 4 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters) with sodium hydride in dimethoxyethane followed by ethyl 4-iodobutyrate gives a yellow oil, b.p. 136°-137°C. (0.16 mm).

EXAMPLE 5 Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixed methyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one (Example 4) with a 20% hydrochloric acid and acetic acid mixture gives a yellow oil.

EXAMPLE 6 Preparation of 2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 3, treatment of 2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluenesulfonic acid monohydrate in ethanol gives a colorless oil, b.p. 93°C. (0.10 mm).

EXAMPLE 7 Preparation of ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentanone carboxylate is reacted with ethyl 7-bromoheptanoate to furnish the subject product, b.p. 147°C. (0.09 mm).

EXAMPLE 8 Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl 2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) is hydrolyzed to furnish the subject product, b.p. 143°C. (0.05 mm).

EXAMPLE 9 Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3, 2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnish the subject product, b.p. 110°C. (0.03 mm).

EXAMPLE 10 Preparation of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one (Example 9) in 250 ml. of acetic anhydride containing 0.940 g. of p-toluenesulfonic acid monohydrate is heated to boiling under partial reflux allowing distillate at 118°C. or less (i.e., acetic acid) to escape through a Vigreaux column equipped with a condenser to collect the distillate. After 16 hours, during which period acetic anhydride is added in portions in order to keep the solvent level at at least 100 ml., the solution is cooled and poured cautiously into a stirred cold mixture of saturated sodium bicarbonate solution (400 ml.) and hexane (250 ml.). The resulting mixture is stirred for an additional 30 minutes during which period solid sodium bicarbonate is added periodically to insure a basic solution. The hexane layer is separated and washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation of the residual oil gives 102 g. (87%) of pale yellow oil, b.p. 118°C. (0.07 mm).

EXAMPLE 11 Preparation of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene

In the manner described in Example 10, treatment of 2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 98°-103°C. (0.35 mm).

EXAMPLE 12 Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene

In the manner described in Example 10, treatment of 2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydride and p-toluenesulfonic acid monohydrate gives a yellow oil, b.p. 109°-110°C. (0.37 mm).

EXAMPLE 13 Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of 1-acetoxy-2 -(6-carbethoxyhexyl)cyclopent-1-ene (Example 10) in 150 ml. of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooled in an ice bath, is added dropwise over a period of about 30 minutes, a solution of 30 g. of bromine in 50 ml. of carbon tetrachloride. After stirring for an additional 45 minutes the chloroform layer is separated and washed successively with dilute sodium thiosulfate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylformamide and added to a mixture of 33 g. of lithium bromide and 32 g. of lithium carbonate in 375 ml. of N,N-dimethylformamide, previously dried by refluxing with 375 ml. of benzene under a Dean-Stark apparatus followed by distillation of the benzene. The mixture is stirred at the reflux temperature for 30 minutes, then cooled and poured into 850 ml. of ice-cold water. The resulting mixture is acidified (cautiously) with 4N hydrochloric acid and extracted with ether three times. The combined ether extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure to afford 41.5 g. of an amber oil. In order to convert any isomeric material to the desired product, 41.5 g. of the above material is treated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450 ml. of absolute alcohol at the reflux temperature for 18 hours. The solution is taken to dryness under reduced pressure. The resulting gum is dissolved in ether and washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness under reduced pressure. The residual oil is distilled to give 30.2 g. of product; b.p. 118°C. (0.05 mm); λ_(max) ^(MeOH) 229 μ(ε9950); λ_(max) 5.75, 5.85, 6.15, 8.45 μ; vapor phase chromatography shows 99% product, containing 1% 2-(6-carbethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of 120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containing approximately 5% of the saturated analogue, and 7.67 g. (10 mole percent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol is stirred at ambient temperatures for 18 hours and is then refluxed for 1 hour. The mixture is cooled, the solvent is evaporated, and the residue is taken up into 150 ml. of chloroform and passed through a column of 450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield a colorless oil containing <0.5% of the saturated impurity.

EXAMPLE 14 Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of 1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene (Example 11) followed by dehydrobromination with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 15 Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene (Example 12) with bromine and subsequent treatment of the brominated product with a mixture of lithium bromide and lithium carbonate in N,N-dimethylformamide is productive of the subject compound. Treatment of this product with p-carboxyphenylhydrazine by the procedure of Example 13 furnishes a product which contains less than 0.5% of the corresponding saturated ketone.

EXAMPLE 16 Preparation of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of 2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13) and 15.0 g. (0.180 mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol is added 25 ml. of pyridine and the resulting solution is stirred for 20 hours at ambient temperatures. The solvent is evaporated and the residue is partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and the solvent is evaporated to yield an oil. Distillation yields 38.7 g. of a colorless oil, b.p. 115°-118°C. (0.075 mm). IR (film): 1740, 1627, 1053, 890 cm.sup.⁻¹. λ_(max) (MeOH) 243 (13,000). NMRδ(CDCl₃): 3.89.

EXAMPLE 17 Preparation of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of 1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200 ml. of benzene under nitrogen is added dropwise 225 ml. of a 25% solution of diisobutyl aluminum hydride in hexane. The resulting solution is stirred for 2 hours at 0°-5°C., poured onto ice and dilute hydrochloric acid, and the aqueous phase is saturated with sodium chloride. The organic phase is separated, washed with saturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. The latter is dissolved in 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p. 62°-64°C. IR (KBr) 3260, 1630, 1059, 893 cm.sup.⁻¹. λ_(max) 243 (14,200). NMR (CDCl₃)δ: 2.37.

EXAMPLE 18 Preparation of 1-methoximino-2-(7-p-toluenesulfonyloxyheptyl)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of 1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml. of dry pyridine at 0°C. is added 8.45 g. (0.0444 mole) of p-toluenesulfonyl chloride and the resulting solution is chilled at 5°C. overnight. The mixture is partitioned between 300 ml. of ice water and diethyl ether. The organic phase is washed with 1:1 ice cold hydrochloric acid, cold water, and cold saturated brine, dried (NaSO₄ /K₂ CO₃), and evaporated under reduced pressure at room temperature to yield an oil. The latter is dissolved in 600 ml. of hexane, treated with 0.5 g. of Darco, filtered and evaporated to yield 7.7 g. of a colorless oil. IR (film) 1600, 1192, 1182, 1053, 890 cm.sup.⁻¹. λ_(max) (MeOH) 228 and 243.

EXAMPLE 19 Preparation of 1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847 g. (0.0368 g. atoms) of sodium; 100 ml. of absolute ethanol, and 7.05 g. (0.0440 mole) of diethyl malonate is added 7.7 g. of the tosylate of Example 18 and the mixture is refluxed for 2 hours under a nitrogen atmosphere. The mixture is partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. The excess diethyl malonate is distilled off under reduced pressure to yield 6.45 g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm.sup.⁻¹.

EXAMPLE 20 Preparation of 1-methoximino-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of Example 19 and 6.72 g. of potassium hydroxide in 150 ml. of 1:1 aqueous methanol is refluxed for 1 hour, cooled, and is partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, and the organic phase is washed with water and saturated brine, dried (Na₂ SO₄) and evaporated to yield a solid. The solid is crystallized from benzene to yield 4.15 g. of tan crystals, m.p. 135°-137°C. (--CO₂).

EXAMPLE 21 Preparation of 1-methoximino-2-(8-carboxyoctyl)-2-cyclopentene

A solution of 3.926 g. (0.0126 mole) of the diacid of Example 20 in 20 ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yield a tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm.sup.⁻¹.

EXAMPLE 22 Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5 hours with 55 ml. of acetone and 20 ml. of 2N hydrochloric acid. The mixture is cooled, the solvent is evaporated, and the residue is partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to yield a tan solid. IR (KBr) 1745, 1665 cm.sup.⁻¹. λ_(max) (MeOH) 228 (12,600).

EXAMPLE 23 Preparation of 2-(8-carbethoxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. of absolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonic acid for 6 hours, cooled, and the solvent is evaporated. The resulting oil is dissolved in 3:1 benzene-ether and the solution is passed through a column of 100 g. of Florisil. The filtrate is evaporated and the residue is distilled to yield 2.97 g. of a colorless oil, b.p. 137°-139°C. (0.05 Torr).

EXAMPLE 24 Preparation of 2-(4-carbethoxybutyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenone (Example 15) with methoxyamine hydrochloride in the manner described in Example 16 gives an oil, b.p. 107°-109°C. (0.05 mm). IR (film): 1740, 1628, 1050, 885 cm.sup.⁻¹. λ_(max) (MeOH) 243 (13,600).

EXAMPLE 25 Preparation of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenomethoxime (Example 24) with diisobutyl aluminum hydride in the manner described in Example 17 gives crystals, m.p. 33°-35°C. IR (KBr) 3420, 1630, 1050, 886 cm.sup.⁻¹. λ_(max) ^(MeOH) 243 (12,020).

EXAMPLE 26 Preparation of 2-(5p-toluenesulfonyloxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime (Example 25) with p-toluenesulfonyl chloride in pyridine in the manner described in Example 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885 cm.sup.⁻¹.

EXAMPLE 27 Preparation of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenone methoxime

To a solution of sodio diethyl ethylmalonate, prepared from 1.63 g. (0.0387 mole) of sodium hydride in mineral oil (57.2%), 100 ml. of ethylene glycol dimethyl ether and 8.5 g. (0.0452 mole) of ethyl diethyl malonate, is added 7.5 g. of tosylate from Example 26 in 20 ml. of ethylene glycol dimethyl ether and the mixture is refluxed for 3 hours and then allowed to stand at room temperature for 18 hours under nitrogen atmosphere. The reaction mixture is filtered and most of the solvent is removed. The mixture is partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated to yield an oil. The excess ethyl diethyl malonate is distilled off under reduced pressure to yield 6.7 g. of a yellow oil. IR (film) 1755, 1728, 1627, 1050, 885 cm.sup.⁻¹.

EXAMPLE 28 Preparation of 2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime

Treatment of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenomethoxime (Example 26) with potassium hydroxide, and 1:1 aqueous methanol in the manner described in Example 20 gives a light yellow oil.

EXAMPLE 29 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime

In the manner described in Example 21, treatment of 2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime (Example 28) with xylene at reflux for 18 hours gives a yellow oil.

EXAMPLE 30 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime (Example 29) with acetone and 2N hydrochloric acid in the manner described in Example 22 gives a light yellow oil.

EXAMPLE 31 Preparation of 2-(6-carbethoxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone (Example 30) with thionyl chloride and then treatment of the acid chloride with ethanol in the usual manner gives an amber oil. The oil is placed on a magnesia-silica gel column and eluted with 3:1 benzene:ether. The solvent is removed and the residue is distilled, b.p. 122°C. (0.06 mm).

EXAMPLE 32 Preparation of diethyl 1,1-dimethyl-5-tetrahydropyranylpentylmalonate

To 486 mg. (0.02 g.-atoms) of magnesium in 5 ml. of toluene containing one molar equivalent of tetrahydrofuran per equivalent of magnesium and one percent iodine (calculated in weight of magnesium) is added dropwise 3.86 g. (0.02 mole) of 4-chloro-1-tetrahydropyranyloxybutane over a period of one hour with stirring, under nitrogen at 70°C. The reaction mixture is stirred at 70°C. for 4 hours. This reagent is then added dropwise to 3 g. (0.015 mole) of ethyl isopropylidenemalonate in 40 ml. of tetrahydrofuran containing 392 mg. of tetrakis [iodo(tri-n-butylphosphine)copper (I)] and stirred at room temperature for 2 hours. The reaction mixture is poured into cold dilute hydrochloric acid and extracted with ether. The ether extract is dried over magnesium sulfate and concentrated to give 5.92 g. of subject product as an oil.

EXAMPLE 33 Preparation of diethyl 1,1-dimethyl-5-hydroxypentylmalonate

A solution of 3.5 g. (0.01 mole) of diethyl 1,1-dimethyl-5-tetrahydrofuranyloxypentylmalonate in 70 ml. of ethanol containing 3 ml. of hydrochloric acid is allowed to stir at room temperature for 18 hours. The solution is concentrated, diluted with water and extracted with ether. The ether extract is washed with water, dried over magnesium sulfate and concentrated to give 3.262 g. of a light yellow oil. The oil is purified by distillation, b.p. 116°-117°C. (0.05 mm).

EXAMPLE 34 Preparation of 3,3-dimethyl-7-hydroxyheptanoic acid

A mixture of 32 g. (0.117 mole) of diethyl 1,1-dimethyl-5-hydroxypentylmalonate, 25 g. of potassium hydroxide and 600 ml. of methanol-water (1:1) is heated at reflux for 8 hours and then allowed to stand at room temperature for 18 hours. The methanol is removed, diluted with water and the reaction mixture is acidified with concentrated hydrochloric acid. The mixture is extracted with ether. The extract is washed with water and saline, dried over anhydrous magnesium sulfate and concentrated to give 27 g. of 1,1-dimethyl-5-hydroxypentylmalonic acid. This crude oil is dissolved in 200 ml. of bis-(2-methoxyethyl)ether and is heated at reflux for 4 hours and then allowed to stand at room temperature overnight. The solvent is removed and the reaction mixture is diluted with water and extracted with ether. The organic solution is washed with saline, dried over magnesium sulfate and concentrated to give 18 g. of product as an oil.

EXAMPLE 35 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3.484 g. (0.02 mole) of 3,3-dimethyl-7-hydroxyheptanoic acid in 25 ml. of chloroform containing 3 drops of dimethylformamide is added 5.8 ml. (0.08 mole) of thionyl chloride and the solution is then heated at reflux for 3-4 hours. The solution is concentrated to give the intermediate 3,3-dimethyl-7-chloro-1-heptanoyl chloride. The acid chloride is dissolved in a minimum amount of benzene and added slowly to 20 ml. benzene, 10 ml. of ethanol and 2.65 ml. of collidine. The solution is heated at reflux for one hour and then concentrated. The residue is dissolved in ether, washed with water, dilute sodium bicarbonate solution and saline. The organic solution is dried over magnesium sulfate and concentrated to give 3.57 g. of product as a yellow oil.

EXAMPLE 36 Preparataion of ethyl 3,3-dimethyl-7-iodoheptanoate

To a solution of 3.57 g. (0.0162 mole) of ethyl 3,3-dimethyl-7-chloroheptanoate in 100 ml. of methyl ethyl ketone is added 4 g. of sodium iodide and the mixture heated at reflux for 18 hours. The reaction mixture is cooled, filtered and concentrated. The residue is partitioned between ether and water. The aqueous phase is extracted several times with ether. The extract is washed with sodium bisulfite solution, water and saline. The organic solution is dried over magnesium sulfate and concentated to give 4.182 g. of a yellow oil. The material is purified by distillation, b.p. 86°-87°C. (0.18 Torr).

EXAMPLE 37 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by treatment of sodio cyclopentanone carboxylate enolate with ethyl 3,3-dimethyl-7-iodoheptanoate by the procedure described in Example 1.

EXAMPLE 38 Preparation of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by decarbalkoxylation of 2-carbalkoxy (mixed methyl and ethyl ester)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one by the procedure described in Example 2.

EXAMPLE 39 Preparation of 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

Esterification of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one with ethanol by the procedure described in Example 3 is productive of the subject compound.

EXAMPLE 40 Preparation of 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

This compound is prepared from 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one and acetic anhydride by the process described in Example 10.

EXAMPLE 41 Preparation of 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

This compound is prepared from 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene via bromination and dehydrobromination according to the procedure described in Example 13.

EXAMPLE 42 Preparation of 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example 16, 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene is prepared from 2-(3-carbethoxypropyl)-2-cyclopentenone (Example 14) and methoxyamine hydrochloride.

EXAMPLE 43 Preparation of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example 17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene and diisobutylaluminum hydride.

EXAMPLE 44 Preparation of 2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 4.833 g. (0.0266 mole) of 2-(4-hydroxypentane)-1-methoximino-2-cyclopentene in 50 ml. of dry tetrahydrofuran under nitrogen is added 16.7 ml. of 1.6 molar n-butyl lithium in hexane, dropwise. The reaction mixture is stirred for 0.5 hour and then 4.85 g. (0.029 mole) of ethyl bromoacetate is added dropwise. The reaction mixture is stirred overnight at room temperature and then refluxed for 1.5 hours. The reaction is cooled and poured into water and extracted several times with ether. The ether extracts are washed with saline, dried over magnesium sulfate, and concentrated. The residue is placed on an alumina column, chloroform being used as a wash solvent. The combined washings are concentrated to dryness to give 4.903 g. of product an a yellow oil.

EXAMPLE 45 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of 2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene with acetone and 2N hydrochloric acid at reflux gives the subject compound as a yellow oil.

EXAMPLE 46 Preparation of 2-(6-carbethoxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 23, treatment of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone with p-toluenesulfonic acid in ethanol produces the subject product as a light yellow oil.

EXAMPLE 47 Preparation of 2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 3.66 g. (0.02 mole) of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene (Example 43) in 50 ml. of 1,2-dimethyoxyethane under nitrogen is added dropwise 17 ml. of 1.6 M n-butyl lithium in hexane. The reaction mixture is stirred for half an hour and then the lithium salt of chloroacetic acid, prepared from 1.89 g. (0.02 mole) of chloroacetic acid and 16 ml. of 1.6M n-butyl lithium in 20 ml. of dimethoxyethane, is added and the reaction mixture is heated at reflux for 48 hours. The solvent is evaporated and the residue is partitioned between ether and water. The aqueous phase is acidified with hydrochloric acid and extracted with ether. The organic phase is washed with water and saturated saline solution, dried (MgSO₄), and evaporated to give 3.35 g. of a yellow oil.

EXAMPLE 48 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopenten-1-one

In the manner described in Example 22, treatment of 2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene (Example 47) with acetone and 2N hydrochloric acid at reflux gives the subject compound as a yellow oil.

EXAMPLE 49 Preparation of 1-methoximino-2-(4-methanesulfonyloxybutyl)-2-cyclopentene

To a solution of 1.83 g. (0.01 mole) of 1-methoximino-2-(4-hydroxybutyl)-2-cyclopentene (Example 43) in 10 ml. of methylene chloride containing 1.52 g. (0.015 mole) of triethylamine is added 1.265 g. (0.011 mole) of methanesulfonyl chloride over a period of 5-10 minutes at -10°--0°C. Stirring is contrinued for 15 minutes and the solution is then washed with cold water, cold 10% hydrochloric acid, cold sodium bicarbonate solution, and cold saline solution. The organic phase is dried (MgSO₄) and concentrated to give an oil which solidifies upon cooling. Crystallization from ether-petroleum ether (30°-60°C.) gives 1.797 g. of white crystals, m.p. 67°-68°C.

EXAMPLE 50 Preparation of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole) of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dry N,N-dimethylformamide is heated at 65°-70°C. for 3 hours. The cooled reaction mixture is poured into water and extracted with diethyl ether. The organic phase is washed with water and saturated saline solution, dried (MgSO₄), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 51 Preparation of 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 50) and 1 g. (0.025 mole) of sodium hydroxide in 50 ml. of 1:1 aqueous-ethanol is refluxed for 48 hours, cooled, and partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with diethyl ether, and the organic phase is washed with water and saturated saline solution, dried (MgSO₄), and evaporated to give 1.86 g. of a yellow oil.

EXAMPLE 52 Preparation of 2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole) 1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 51) in 44 ml. of acetone and 13.1 ml. of 2N hydrochloric acid is refluxed for 5 hours. The solvent is partially evaporated and a solid precipitates and is collected. The residue is extracted with diethyl ether and the organic phase is washed with saturated saline solution, dried (MgSO₄), and evaporated to yield additional solid. The combined solid material is crystallized from ether/pet ether (30°-60°C°) to yield crystalline material, m.p. 70°-72°C.

EXAMPLE 53 Preparation of 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of 2(5-carboxypentyl)-2-cyclopentenone (Example 52) and 90 mg. of p-toluensulfonic acid in 150 ml. of ethanol is refluxed for 18 hours. The solvent is evaporated and the residue is dissolved in ether. The organic phase is washed with water, sodium bicarbonate solution, and saturated saline solution, dried (MgSO₄), and evaporated to give 1.371 g. of a light yellow oil.

EXAMPLE 54 Preparation of 2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxycyclopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0 moles) of cyclopentanone carboxylate (methyl and ethyl esters) and 200 g. (8.3 moles) of mineral oil free sodium hydride in 10 l. of 1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate [M. E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947)], and 1200 g. (8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours. The mixture is cooled, concentrated to 4 l. and partitioned between dilute hydrochloric acid and diethyl ether. The organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated to yield 1920 g. of an oil.

EXAMPLE 55 Preparation of 2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxypentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of 2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example 54), 2.2 l. of glacial acetic acid, 1 l. of concentrated hydrochloric acid, and 1 l. of water is refluxed for 18 hours, cooled, and partitioned between saturated brine and benzene. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated in vacuo to yield 3155 g. of an oil.

EXAMPLE 56 Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene

A solution of 400 g. (2.04 moles) of a mixture of 2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone (Example 55) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 l. of acetic anhydride is refluxed at a rate to maintain a steady distillation of acetic acid from the reaction through a helix -packed fractionation column. The reaction is continued with the addition of acetic anhydride to maintain a constant volume until complete conversion of starting materials to product is evident. The mixture is cooled and partitioned between 2 l. of hexane and 3 l. of cold water containing solid sodium bicarbonate to maintain a neutral pH. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to yield 452 g. of an oil.

EXAMPLE 57 Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate, 3 l. of water, and 2.5 l. of chloroform cooled to 5°C. is added simultaneously 1016 g. (4.0 moles) of 1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 56) and a solution of 648 g. (4.05 moles) of bromine in 500 ml. of carbon tetrachloride at a rate to maintain a temperature below 10°C. The mixture is stirred for half an hour after addition of the reagents and the phases are then separated. The organic phase is washed with 2% sodium thiosulfate solution, water, and saturated brine, dried (MgSO₄), and evaporated in vacuo to an oil. the oil is immediately added to a refluxing slurry of 500 g. (5.0 moles) of calcium carbonate in 2.5 l of N,N-dimethylacetamide under nitrogen and the mixture is then refluxed for thirty minutes. The mixture is cooled, filtered, and partitioned between water and diethyl ether. The organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated to yield 757 g. of an oil, b.p. 116°-118°C. (0.25 mm.).

EXAMPLE 58 Preparation of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16, 2-(5-acetoxypentyl)-2-cyclopentenone (Example 57) is treated with methoxyamine hydrochloride in pyridine and ethanol to yield the subject compound, b.p. 101°-103°C. (0.20 mm.).

EXAMPLE 59 Preparation of 1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of 1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 58) and 56 g. (1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol is refluxed for 2 hours and then cooled. The solvent is partially removed in vacuo and the residue is partitioned between saturated brine and diethyl ether. The organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to yield an oil which crystallized, m.p. 35°-36°C.

EXAMPLE 60 Preparation of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of 1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene (Example 59) and 7.6 g. (0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10°C. is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate to maintain a temperature of -10° to 0°C. The mixture is then stirred for 15 minutes and then poured into ice water. The organic phase is washed with cold 10% hydrochloric acid, cold saturated sodium bicarbonate solution, and cold saturated brine, dried (MgSO₄), and evaporated to yield a solid, m.p. 78°-80°C.

EXAMPLE 61 Preparation of 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of sodiodiethylmalonate in 1,2-dimethoxyethane, prepared from 248 g. (1.55 moles) of diethyl malonate and 17.2 g. (0.95 mole) of mineral oil free sodium hydride in 1 l. of 1,2-dimethoxyethane under nitrogen, is added 170 g. (0.62 mole) of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) in 1.5 l. of 1,2-dimethoxyethane and the mixture is refluxed for 5 hours. The mixture is cooled, filtered, and the solvent is evaporated. The residue is partitioned between cold dilute hydrochloric acid and water, and the organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to remove solvent and excess diethyl malonate to yield 209 g. of an oil.

EXAMPLE 62 Preparation of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20, 1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cylcopentene is treated with potassium hydroxide in 1:1 aqueous methanol and then hydrochloric acid to yield the desired compound as crystals from diethyl ether, m.p. 110°-115°C.

EXAMPLE 63 Preparation of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of 1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. of bis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, and evaporated to yield an oil. The latter is crystallized from hexane to yield 92 g. of solid, m.p. 70°-72°C.

EXAMPLE 64 Preparation of 2(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of 1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 63) with acetone and 2N hydrochloric acid at reflux provides the subject compound.

EXAMPLE 65 Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 64) in the manner of Example 23 provides the subject compound.

EXAMPLE 66 Preparation of 1-methoximino-2-(6-fluoro-6,6-dicarbethoxyhexyl)-2-cyclopentene

To a solution of sodiodiethyl fluoromalonate, prepared from 2.062 g. (0.0491 mole) of sodium hydride in mineral oil (57.2%), 40 ml. of dry N,N-dimethylformanide and 8.174 g. (0.0458 mole) of diethyl fluoromalonate is added dropwise 11.32 g. (0.0413 mole) of 1-methoximino-2-(5-methylsulfonyloxypentyl)-2-cyclopentene (Example 60) in 60 ml. of N,N-dimethylformamide. The mixture is refluxed for 2 hours under a nitrogen atmosphere. The mixture is concentrated and partitioned between cold dilute hydrochloric acid and diethyl ether, and the organic phase is washed with saturated brine, dried (MgSO₄), and evaporated to yield 13.631 g. (92%) of a yellow oil.

EXAMPLE 67 Preparation of 1-methoximino-2-(6-fluoro, 6,6-dicarboxyhexyl)-2cyclopentene

A mixture of 13.631 g. of the diester of Example 66 and 16 g. of potassium hydroxide in 364 ml. of 1:1 aqueous methanol is refluxed for 5 hours, cooled, concentrated, and is partitioned between water and diethyl ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, and the organic phase is washed with saturated brine, dried (MgSO₄) and evaporated to yield a solid. The solid is crystallized from diethyl ether petroleum ether (30°-60°C.) to give 10 g. (90%) of white crystals, m.p. 143°-145°C. (-CO₂).

EXAMPLE 68 Preparation of 1-methoximino-2-(6-fluoro-6-carboxyhexyl)-2-cyclopentene

A solution of 10 g. of the diacid of Example 67 in 60 ml. of 2-methoxyethyl ether is refluxed for 7 hours, cooled, and evaporated to yield 8.5 g. (95%) of a tan solid. A sample is crystallized from diethyl ether-petroleum ether (30°-60°C.) to give white crystals, m.p. 98°-100°C.

EXAMPLE 69 Preparation of 2-6-fluoro-6-carboxyhexyl)cyclopent-2-en-1-one

The acid methoxime (8.5 g.) from Example 68 is refluxed for 5 hours with 180 ml. of acetone and 64 ml. of 2N hydrochloric acid. The mixture is cooled, the solvent is evaporated, and the residue is partitioned between water and diethyl ether. The organic phase is washed with saturated brine, dried (MgSO₄) and evaporated to yield 7.4 g. (98%) of a light yellow oil.

EXAMPLE 70 Preparation of 2-(6-fluoro-6-carbethoxyhexyl)cyclopent-2-en-1-one

The acid ketone (7.4 g.) from Example 69 is Fisher esterified with 300 ml. of absolute ethanol and 400 mg. of p-toluenesulfonic acid for 18 hours, cooled, and the solvent is evaporated. The resulting oil is dissolved in ether, washed with dilute sodium bicarbonate solution, and saline, dried (MgSO₄), and evaporated to give 7.306 g. (86%) of a light yellow oil.

EXAMPLE 71 Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatment of 1 methoximino-2-(7-p-toluenesulfonyloxy)-2-cyclopentene (Example 18) with sodium cyanide in the manner of Example 50 is productive of the subject compound.

EXAMPLE 72 Preparation of 2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximono-2-cyclopentene (Example 71) by the procedure of Example 51 is productive of the subject compound.

EXAMPLE 73 Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 72 with acetonehydrochloric acid by the procedure of Example 52 is productive of the subject compound.

EXAMPLE 74 Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 73 by the procedure of Example 53 is productive of the subject compound.

EXAMPLE 75 Preparation of 2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60) with sodio diethyl phenylmalonate by the procedure of Example 61 is productive of the subject compound.

EXAMPLE 76 Preparation of 2-(6,6-dicarboxy-6-phenylhexyl)-2-methoximono-2-cyclopentene

Alkaline hydrolysis of 2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 75) by the procedure of Example 20 is productive of the subject diacid.

EXAMPLE 77 Preparation of 2-(6-phenylhexyl)-1-methoximino-2-cyclopentene

Decarboxylation of 2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 76) by the procedure of Example 63 is productive of the subject compound.

EXAMPLE 78 Preparation of 2-(6-carboxy-6-phenylhexyl)-2-cyclopentene-1-one

Methoxime cleavage of 2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 77) in the manner of Example 69 is productive of the subject ketone.

EXAMPLE 79 Preparation of 2-(6-carbethoxy-6-phenylhexyl)-2-cyclopenten-1-one

Fisher esterification of the carboxylic acid of Example 78 in the manner of Example 70 is productive of the subject keto-ester.

EXAMPLE 80 Preparation of 2-(6-fluoro-6,6-dicarbethocyhexyl)-1-methoximino-2-cyclopentene

An ethanolic solution of sodium ethoxide, prepared from 0.389 g. of sodium and 40 ml. of absolute ethanol, is treated at ambient temperatures with 5.05 g. of 2-(6,6-dicarbethoxyhexyl)-1-methoximino-2-cyclopentene (Example 61). The resulting solution is cooled to -20°C. and then treated with a stream of perchloryl fluoride until the mixture becomes neutral. The excess perchloryl fluoride is removed with a stream of nitrogen and the mixture is retreated with 10 ml. of an ethanolic solution of sodium ethoxide (from 0.350 g. of sodium) and then with perchloryl fluoride until the mixture becomes neutral. The excess perchloryl fluoride is removed with a stream of nitrogen and the mixture is filtered and evaporated to an oil. The latter is partitioned between ether and water and the organic phase is washed with saturated saline, dried (Na₂ SO₄) and evaporated to afford the subject compound.

EXAMPLE 81 Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465 (1966)] in 1400 ml. of n-butanol containing 2.7 g. of p-toluenesulfonic acid monohydrate is allowed to stand at room temperature in a stoppered flask for about 24 hours. The solution is taken to dryness. The residue is taken up in ether and the ethereal solution is washed several times with saline solution, dried with anhydrous magnesium sulfate, and taken to dryness to afford the subject butyl ester.

EXAMPLES 82-84

Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one by the precedure of Example 81 with the appropriate alcohol affords the ester of the following table.

                  TABLE IV                                                         ______________________________________                                         Ex.  Alcohol    Product Ester                                                  ______________________________________                                         82   isopropanol                                                                               2-(6-carboisopropoxyhexyl)cyclopent-2-                         en-1-one                                                                       83   methanol   2-(6-carbomethoxyhexyl)cyclopent-2-en-                         1-one                                                                          84   1-hydroxy- 2-(6-carbo-n-decyloxyhexyl)cyclopent-2-                        n-decane                                                                       en-1-one                                                                       ______________________________________                                    

EXAMPLE 85 Preparation of diethyl (5-chloro-1,1-dimethylpentyl)malonate

To magnesium (71 g. 2.92 moles) under 1 l. of ether containing a few crystals of iodine is added dropwise 1-chloro-4-bromobutane (500 g., 2.92 moles) over a period of 30 minutes with stirring under nitrogen. The reaction is maintained at a temperature of 0°C. to 5°C. by immersing in an acetone-Dry Ice bath periodically. After stirring for 30 minutes at room temperature, the solution is chilled to below 0°C. and is then transferred to a dropping funnel from which it is added dropwise to diethyl isopropylidene malonate (440 g., 2.19 moles) [A. C. Cope and E. M. Hancock, J.A.C.S. 60, 2644 (1938)] dissolved in 1000 ml. of ether containing the tri(n-butyl)phosphine complex of copper (I) iodide (57g.) [G. B. Kaufman and L. A. Teter, Inorganic Synthesis, 7, 9(1963)] at -10°C. with stirring under nitrogen over a period of 2 hours. After stirring at room temperature for 4 hours, the reaction mixture is poured into cold dilute hydrochloric acid and is extracted with ether. The combined ether extracts are washed with saline solution, dried over magnesium sulfate, and concentrated in vacuo to give 700 g. of crude amber oil, which is distilled under vacuum to yield two fractions: 212.4 g. with b.p. at 110°C-135°C. at 0.3 mm. and 100.0 g. with b.p. at 135°C.-145°C. at 0.3 mm. The total yield is 312.4 g. (49%).

EXAMPLE 86 Preparation of 3,3-dimethyl-7-chloroheptanoic acid

A mixture containing diethyl 5-(5-chloro-1,1-dimethylpentyl)malonate (648 g., 2.22 moles) potassium hydroxide (460 g.) and eight liters of 1:1 isopropanol: water is stirred at room temperature overnight. Most of the isopropanol is distilled and the residue is diluted with water, and then carefully acidified with conc. hydrochloric acid. The mixture is extracted with ether and the extracts are washed with water and saline, dried over magnesium sulfate and concentrated in vacuo to give 548 g. of crude oil. The oil is dissolved in 3 liters of diglyne which is heated under reflux for 16 hours. About 2.7 l. of solvent is distilled, and the remainder is diluted with water and extracted with ether. The extracts are washed with saline, dried over magnesium sulfate and concentrated in vacuo to give 428 g. of crude oil (99%).

EXAMPLE 87 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3,3-dimethyl-7-chloroheptanoic acid (428 g., 2.21 moles) in 3 l. of chloroform containing 3 ml. of N,N-dimethylformamide is added 500 ml. of thionyl chloride and the resulting solution is tested under reflux for 3 hours. The reaction solution then is concentrated in vacuo and the residual acid chloride is dissolved in a minimum amount of benzene and added slowly to a solution containing 1260 ml. of 95% ethanol and 2520 ml. of benzene and 390 ml. of collidine. After heating under reflux for one hour, the solution is concentrated and the residue is dissolved in ether washed with water, dilute sodium bicarbonate solution and saline solution, dried over magnesium sulfate and concentrated to give 415 g. of crude oil, which is distilled under vacuum to yield two fractions: 46.6 g. boiling at 75°C. (0.3 mm.) and 236.7 g. boiling at 75°C. - 80°C (0.3 mm). The total yield is 283.3 g. (60%) and the product is indicated to be 95% pure by g.l.c.

EXAMPLE 88 Preparation of methyl/ethyl 2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate

Sodium hydride (67 g., 1.55 moles) is placed in a three l. round-bottom flask and to this is added 1.1 liters of glyme from a dropping funnel under nitrogen flow and with stirring. To the resulting grayish mixture is added the 2-carbalkoxycyclopentanone (mixed methyl and ethyl esters) dropwise over a period of 45 minutes with nitrogen flow whilst the temperature is maintained in the range of 40°-55°. Ethyl 3,3-dimethyl-7-chloroheptanoate (283 g., 1.28 moles) and potassium iodide (195 g., 1.32 moles) are added and the mixture is heated at reflux overnight. After most of the solvent is distilled, the residue is made acidic with dilute hydrochloric acid and is then extracted with ether. The ether extracts are washed with water and saline solution, dried over magnesium sulfate, and concentrated in vacuo to 500 g. of crude yellow oil, which is distilled to give 405 g. (94% yield) of oil with b.p. 140°-180° (0.8 mm).

EXAMPLE 89 Preparation of 7-(2-Cyclopentanone)-3,3 dimethylheptanoic acid

Methyl/Ethyl 2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate (200 g., 0.6 moles), glacial acetic acid (180 ml) and 240 ml. of diluted hydrochloric acid, prepared from 100 ml. of conc. hydrochloric acid and 300 ml. of water, are placed in a 2 l. flask, containing a reflux condenser and a magnetic stirrer. The mixture then is stirred at reflux for 24 hours. The reaction mixture is cooled, 1 l. of water is added and the mixture is extracted several times with benzene. The organic extracts are combined, washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to an oil (173.5 g.). The oil is rendered basic with sodium hydroxide solution, extracted with benzene and made acidic with hydrochloric acid and reextracted with benzene several times. The benzene layers are combined and washed with water, saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to yield 109.8 g. (78%) of crude oil which was used without further purification in the next step.

EXAMPLE 90 Preparation of Ethyl 7-(2-Cyclopentanone)-3,3-dimethylheptanoate

To a solution of 7-(2-cyclopentanone)-3,3-dimethylheptanoic acid (45 g., 0.22 mol.) in 285 ml. of chloroform containing three drops of N,N-dimethylformamide is added dropwise 25 ml. of thionyl chloride. The solution is stirred at room temperature for 20 minutes, the solvent is removed at reduced pressure and the residual acid chloride is dissolved in a minimum amount of benzene and added slowly to a solution containing 115 ml. of ethanol, 230 ml. benzene and 30 ml. of collodine. This solution is heated under reflux for 15 minutes and then concentrated. The residue is dissolved in ether, washed with water, diluted sodium bicarbonate solution and saline solution, dried over magnesium sulfate and concentrated to give 51 g. of crude oil. Distillation gives 40 g. (67%) b.p. 135°-145° (0.1 mm.) of oil.

EXAMPLE 91 Preparation of 1-Acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

A solution of ethyl 7-(2-cyclopentanone)-3,3-dimethylheptanoate (90 g., 0.336 mol.) and p-toluenesulfonic acid (0.94 g.) in 250 ml. of acetic anhydride is heated to boiling under partial reflux, allowing distillate at 118° or less (i.e. acetic acid) to escape thru a Vigreux column equipped with a condenser to collect the distillate. After ten hours 130 ml. of distillate is collected. Another 50 ml. of acetic anhydride is added and the reaction is heated for five more hours; an additional 125 ml. of acetic anhydride is added, the reaction is heated for seven more hours; finally another 50 ml. of acetic anhydride is added and heating is continued for 4 more hours. The solution is cooled and poured (cautiously) into a cold (0°-5°) mixture of saturated aqueous sodium bicarbonate (400 ml.) and hexane (250 ml.). The resulting cold mixture is stirred for thirty minutes during which time portions of solid sodium bicarbonate are added periodically until carbon dioxide evaluation ceases. The hexane layer is separated and washed with saturated sodium chloride solution until the washings are neutral, dried over magnesium sulfate and treated with Darco decolorizing charcoal for clarification and then evaporated to dryness leaving an amber colored oil (87.5 g., 84%).

EXAMPLE 92 Preparation of 2-(6-Carboxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene (35 g., 0.113 mole) chloroform (95 ml.), water (125 ml.) and calcium carbonate (11.8 g.) cooled in an ice-bath is added dropwise over a period of 30 minutes a solution of bromide (18.8 g.) in carbon tetrachloride (31 ml.). After stirring in the cold for an additional 45 minutes the orange colored chloroform layer is separated and washed with dilute sodium bisulfite and saturated saline solution, dried over magnesium sulfate and taken to dryness in vacuo (bath temperature: 35°-40°) leaving an amber colored oil. A slurry of 100 ml. of N,N-dimethylacetamide and 16.5 g. of CaCO₃ is stirred and heated to reflux under nitrogen flow. The above dried oil is added from a dropping funnel rapidly, maintaining reflux and nitrogen flow for 30 minutes. The cooled reaction mixture is filtered, and the precipitate is washed with ether. The filtrate is poured into two liters ice-cold water and is extracted with ether. The combined extracts and washing is washed with water, saturated saline, treated with decolorizing charcoal, filtered. The solvent evaporated in vacuo to give 24 g. (77%) of subject product.

EXAMPLE 93 Preparation of 4-bromo-2(6-carboxyhexyl)cyclopent-2-en-1-one

A stirred mixture of 35.9 g. (0.171 moles) of 2-(6-carboxyhexyl) cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465 (1966)], 35.0 g. (0.197 moles) of N-bromosuccinimide, and 600 ml. of carbon tetrachloride is refluxed for 35 minutes. The mixture is cooled to 5°C. and filtered. The filtrate is washed with cold water, dried over magnesium sulfate, and taken to dryness to give an oil, λ^(MeOH) _(max). = 225 mμ (8850); νmax. = 1705 (carbonyl groups) and 1625. cm⁻ ¹ (olefin group).

EXAMPLE 94 Preparation of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one

To a stirred solution of 10.6 g. (ca. 34 mmoles) of crude 4-bromo-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 93) in 100 ml. of acetone and 65 ml. of water is added 8.80 g. (45.2 mmoles) of silver fluoborate during 2 minutes. The temperature is maintained at 25°-30°C. by external cooling. The mixture is stirred for 90 minutes, filtered, saturated with sodium chloride, and extracted with ether. The extract is extracted with half saturated sodium bicarbonate solutions. The basic solutions is reacidified with dilute hydrochloric acid, saturated with sodium chloride, and extracted with ether. the extract is washed with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The crude product is purified by partition chromatography on Celite to give an oil; λ^(MeOH) _(max). = 233 mμ. (7360); νmax. = 3380 (hydroxyl groups), 1710 (carbonyl groups), and 1632 cm⁻ ¹ (olefin group).

EXAMPLE 95 Preparation of 4-tetrahydropyranyloxy-2-(6-tetrahydropyranylcarboxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 5.59 g. (24.6 mmoles) of 4-hydroxy-2-(6-carboxyhexyl) cyclopent-2-en-1-one (Example 94) and 20.7 g. (246 mmoles) of dihydropyran in 100 ml. of methylene chloride at 20°C is added 47 mg. (0.246 mmoles) of p-toluenesulfonic acid monohydrate in one portion. The temperature is maintained at 20°-25°C. by cooling and is stirred for one hour at that temperature. The solution is diluted with 200 ml. of ether and poured into a mixture of 40 ml. of saturated sodium bicarbonate solution, 40 ml. of saturated sodium chloride solution, and 80 ml. of water. The phases are separated, and the aqueous phase is extracted with additional ether. The total extract is washed successively with water and saturated sodium chloride solution, dried over potassium carbonate, and freed of volatile matter by concentration at reduced pressure to give an oil, λ^(MeOH) _(max). = 223 mμ (9500); νmax. 1730 (ester carbonyl group), 1705 (ketone carbonyl group), and 1030 cm⁻ ¹ (tetrahydropyranyloxy groups).

EXAMPLE 96 Preparation of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime

The subject compound is prepared from sodio diethyl methylmalonate and 2-(5-methanesulfonyloxypentyl)-2-cyclopentenone methoxime (Example 60) by the procedure described in Example 61.

EXAMPLE 97 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime

Saponification of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime (Example 96) with potassium hydroxide by the method of Example 20 is productive of 2-(6,6-dicarboxyheptyl)-2-cyclopentenone methoxime, decarboxylation of which in the manner of Example 83 provides the subject compound.

EXAMPLE 98 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone

Methoxime cleavage of 2-(6-carboxyheptyl)-2-cyclopenteneone methoxime (Example 97) in the manner of Example 22 provides the subject ketone.

EXAMPLE 99 Preparation of 2-(6-carbethoxyheptyl)-2-cyclopentenone

Esterification with ethanol of the acid chloride derived from 2-(6-carboxyheptyl)-2-cyclopentenone in the manner of Example 31 is productive of the subject compound.

EXAMPLE 100 Preparation of ethyl (methyl) 7-(2- carbethoxycyclohexan-1-on-2-yl)heptanoate

To a stirred suspension of 51 g. of sodium hydride (57% in mineral oil) in 675 ml. of dimethylformamide is added 200 g. of 2-cyclohexanone carboxylate (60% ethyl - 40% methyl esters) over a 1-5 hr. period with external cooling to maintain the temperature at 20°-25°C. The reaction mixture is stirred at ambient temperature for 15 minutes and heated to 50°C. over 15 minutes. To the stirred mixture is added 300 g. of ethyl 7-bromoheptanoate during a 10 minute period. The reaction mixture is stirred at 50°-60°C. for 4 hours, cooled, and poured into water. The product is obtained by ether extraction. The extract is washed successively with water and saturated sodium chloride, dried and evaporated to give a liquid which is purified by distillation, IR 1735 cm⁻ ¹ (ester carbonyls) and 1710 cm⁻ ¹ (ketone carbonyl).

EXAMPLE 101 Preparation of 7-(cyclohexan-1-on- 2-yl)heptanoic acid

A stirred mixture of 380 g. of mixed methyl and ethyl esters of 7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate (Example 10), 202 ml. of concentrated sulfuric acid, 970 ml. of glacial acetic acid, and 970 ml. of water is refluxed for 22.5 hours. The cooled reaction mixture is treated with 380 g. of sodium carbonate and 2 liters of water and is extracted with ether. Acidic material is partitioned from the ether extract with 1.0M sodium carbonate. The aqueous phase is acidified with concentrated hydrochloric acid and extracted with ether. The extract is washed successively with water and saturated sodium chloride, dried, and evaporated to give an oil.

EXAMPLE 102 Preparation of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate

A solution of 232 g. of 7-(cyclohexan-1-on-2-yl)heptanoic acid in 2500 ml. of ethanol is refluxed for 4.5 hours with 3.8 g. of p-toluenesulfonic acid monohydrate. The solution is diluted with 200 ml. of benzene, and boiling is continued for 2 hours as 200 ml. of distillate is removed. The volume of the solution is concentrated to 500 ml. After dilution with 500 ml. of ether the solution is extracted with a solution prepared from 50 ml. of saturated sodium bicarbonate, 50 ml. of saturated sodium chloride, and 100 ml. of water. The extract is washed with saturated sodium chloride, dried, and evaporated. The product is purified by distillation to give a liquid, IR 1740 cm⁻ ¹ (ester carbonyl) and 1715 cm⁻ ¹ (ketone carbonyl).

EXAMPLE 103 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one

The subject compound is prepared in the manner described in Example 10 by treatment of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with sodium hydride and ethyl 4-iodobutyrate.

EXAMPLE 104 Preparation of 2-(3-carbethoxypropyl)cyclohexan-1-one

This compound is prepared from 2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one (Example 13) by decarbalkoxylation according to the procedure described in Example 11 followed by esterification by the procedure of Example 12.

EXAMPLE 105 Preparation of 2-(5-carbethoxypentyl)cyclohexan-1-one

This compound is prepared by alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with ethyl 6-bromohexanoate according to the procedure of Example 10, followed by decarbalkoxylation according to the procedure of Example 11 and finally esterification by the procedure of Example 12.

EXAMPLE 106 Preparation of 2-(7-carbethoxyheptyl)cyclohexan-1-one

Alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethyl esters) with ethyl 8-bromoctanoate in accordance with the procedure of Example 10, followed by decarbalkoxylation by the procedure of Example 11 and then esterification by the procedure of Example 12 is productive of the subject compound.

EXAMPLE 107 Preparation of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate

A stirred solution of 28.0 g. of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate (Example 12), 170 mg. of p-toluenesulfonic acid monohydrate, and 25.6 g. of acetic anhydride is heated for 5 hours while allowing 8.0 g. of distillate to distill. The cooled solution is poured into a stirred, ice-cold mixture of 500 ml. of saturated sodium bicarbonate and 250 ml. of hexane. After 1 hour the hexane phase is separated, dried, and evaporated. The crude product is distilled to give a liquid, IR 1760 cm.sup.⁻¹ (vinyl ester carbonyl) and 1740 cm.sup.⁻¹ (ethyl ester carbonyl).

EXAMPLE 108 Preparation of 1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene

Treatment of 2-(3-carbethoxypropyl)cyclohexan-1-one (Example 14) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 109 Preparation of 1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene

Treatment of 2-(5-carbethoxypentyl)cyclohexan-1-one (Example 15) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 110 Preparation of 1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene

Treatment of 2-(7-carbethoxyheptyl)cyclohexan-1-one (Example 16) with acetic anhydride by the procedure of Example 24 is productive of the subject compound.

EXAMPLE 111 Preparation of ethyl 7-(cyclohex-2-en-1-one-2-yl)heptanoate

To a stirred solution of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate (Example 24) in 750 ml. of acetic acid and 125 ml. of pyridine at 10°C. is added a solution of 13.8 g. of bromine in 200 ml. of acetic acid over 20 minutes. The resulting solution is allowed to stand at ambient temperature for 45 minutes and is then decolorized with sodium sulfite. The solution is poured into 800 ml. of half-saturated sodium chloride and extracted with 1:1 hexane-ether. The extract is washed successively with water and saturated sodium chloride, dried over sodium carbonate, and evaporated to give 32 g. of the crude bromoketone. To a stirred suspension of 14.2 g. of lithium bromide and 16.6 g. of lithium carbonate in 250 ml. of anhydrous dimethylformamide at 80°C. is added to the above bromoketone. The stirred mixture is heated to boiling over 20 minutes and refluxed for 15 minutes. The cooled mixture is poured into 1000 ml. of water, acidified with dilute hydrochloric acid, and extracted with ether. The extract is washed successively with water and saturated sodium chloride, dried, and evaporated. The product is purified by distillation to give a liquid, IR 1740 cm.sup.⁻¹ (ester carbonyl), 1685 cm.sup.⁻¹ (ketone carbonyl), and 1650 cm.sup.⁻¹ (olefin); NMR (CCl₄) 6.63 (multiplet, vinyl proton).

EXAMPLE 112 Preparation of 2-(3-carbethoxypropyl)cyclohex-2-en-1-one

In accordance with the procedure of Example 40, bromination of 1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene (Example 25) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 113 Preparation of 2-(5-carbethoxypentyl)cyclohex-2-ene-1-one

By the procedure of Example 40, bromination of 1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene (Example 26) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 114 Preparation of 2-(7-carbethoxyheptyl)cyclohex-1-en-2-one

By the procedure of Example 40, bromination of 1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene (Example 27) followed by treatment with lithium bromide and lithium carbonate is productive of the subject compound.

EXAMPLE 115 Preparation of 2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene

In the manner described in Example 34, treatment of 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene with p-toluene sulfonyl chloride in pyridine gives the subject product as a light yellow oil; IR (film): 1600, 1190, 1050, 885 cm.sup.⁻¹.

EXAMPLE 116 Preparation of 2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene

To a stirred mixture of 1.465 g. (0.0348 mole) of sodium hydride (57.2% in mineral oil) in 50 ml. of dimethoxyethane, under nitrogen, is added slowly 4.8 g. (0.0347 mole) of ethyl-2-mercaptoacetate. The reaction mixture is stirred at room temperature for one hour and then a solution of 7.8 g. (0.0231 mole) of 2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene in 30 ml. of dimethoxyethane is added dropwise and stirred at room temperature for 18 hours. The solution is heated at reflux for 1 hour, cooled and poured into cold dilute hydrochloric acid and then extracted with ether. The combined ether extracts are washed with saline, dried over magnesium sulfate and evaporated to give 7.6 g. of subject product as a yellow oil.

EXAMPLE 117 Preparation of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 38, treatment of 2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene with acetone and 2N hydrochloric acid at reflux gives the subject product as a yellow oil.

EXAMPLE 118 Preparation of 2-(6-carbethoxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 39, treatment of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone with p-toluenesulfonic acid in ethanol gives the subject ester as a yellow oil.

EXAMPLE 119 Preparation of 3-triphenylmethoxy-1-octyne

A mixture of 1.26 g. (10.0 mmoles) of 1-octyn-3-ol, 4.85 g. (15.0 mmoles) of triphenylmethyl bromide, and 50 ml. of dry pyridine is heated at 95°C. for 60 minutes with occasional swirling. The solution is cooled, treated with water, and extracted with ether. The extract is washed successively with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The crude product is purified by chromatography on Florisil and recrystallization from petroleum ether to give white crystals, m.p. 65°-66.5°, ν max. (KBr) 3280 (acetylenic hydrogen), 1605, 1030, and 702 cm.sup.⁻¹ (triphenylmethoxy group).

EXAMPLE 120 Preparation of ethyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate

A stirred solution of 7.37 g. (20.0 mmoles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of benzene is treated with 16.7 mg. of 1.2 M diisobutylaluminum hydride in hexane, and the resulting solution is heated at 50°C. for 2 hours. The solution is cooled to 0°C. and treated with 10.5 ml. of 1.7 M methyl lithium in ether. After stirring for a 20 minute period at ambient temperature, the alanate solution is cooled to 0°C. and treated with a solution of 3.98 g. (16.7 mmoles) of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 13) in 5 ml. of ether. The resulting solution is stirred at ambient temperature for 22.5 hours, diluted with ether, and poured into a stirred mixture 2N acetic acid and ice. After stirring until methane evolution ceases, the organic phase is separated and washed successively with water and saturated sodium chloride solution. The extract is dried over magnesium sulfate and concentrated. The crude product in the residue is purified by chromatography on silica gel to give an oil, ν max. 1735 (carbonyl groups), 967 (trans vinyl group), and 705 cm.sup.⁻¹ (triphenylmethoxy group).

EXAMPLE 121 Preparation of ethyl 15-hydroxy-9-oxo-13-trans-prostenoate

A 0.05M solution of ethyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate (Example 120) in glacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45°C. for 3.5 hours. The solvents are evaporated at reduced pressure, and the residue is dissolved in ether. The solution is washed successively with water, 0.5N sodium bicarbonate solution, and saturated sodium chloride solution; dried over magnesium sulfate; and concentrated. Column chromatography of the crude product on silica gel gives two epimeric substances which are purified separately by thin layer chromatography to give oils differing only in chromatographic behavior, ν max. 3470 (hydroxy group), 1735 (carbonyl groups), and 967 cm.sup.⁻¹ (trans vinyl group).

EXAMPLE 122 Preparation of 15-hydroxy-9-oxo-13-trans-prostenoic acid

A solution of 2 g. of ethyl 15-hydroxy-9-oxo-13,14-trans-prostenoate (Example 121) (mixture of racemates) in 32 ml. of methanol-water (1:1), containing 850 mg. of potassium hydroxide is stirred at ambient temperature for 18 hours. After acidification with 10% hydrochloric acid, the solution is extracted with ether several times. The combined ether extracts are washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give 1.69 g. (92%) of an oil which partially crystallizes. Recrystallized from etherhexane gives white crystals, m.p. 79°-81°C.; nmr δ 6.36 (s, hydroxyl and carboxyl groups), 5.61 (t, olefinic protons), 4.12 (s, C₁₅ -H) and 0.90 (s, terminal methyl).

EXAMPLE 123 Preparation of tetrahydropyran-2-yl 9-oxo-11-tetrahydropyranyloxy- 15-triphenylmethoxy-13-trans-8ξ-prostenoate

In the manner described in Example 120, 13.6 g. (37 mmoles) of 3-triphenylmethoxy-1-octyne (Example 119) contained in 18.5 ml. of benzene in converted to an alanate reagent by treatment with 31 ml. of 1-2M diisobutylaluminum hydride in hexane and 21 ml. of 1.7M methyl lithium in ether. To the stirred, ice-cold reagent is added a solution of 10.97 g. (24.6 mmoles) of 2-(6-tetrahydropyranylcarboxyhexyl)-4-tetrahydropyranyloxycyclopent-2-en-1-one (Example 95) in 10 ml. of ether during 10 minutes. The resulting solution is stirred at ambient temperature for 20 hours, diluted with ether, and poured into a stirred mixture of 2N hydrochloric acid and ice. The organic phase is separated and washed successively with water and saturated sodium chloride solution. The extract is dried over magnesium sulfate, and the solvents are evaporated at reduced pressure to give the crude product as an oil, ν max. 1735 (carbonyl groups), 1030 (tetrahydropyranyloxy groups), 970 (trans vinyl group), and 705 cm.sup.⁻¹ (triphenylmethoxy group).

EXAMPLE 124 Preparation of 11,15-dihydroxy-9-oxo-13-trans-prostenoic acids

A 0.05M solution of crude tetrahydropyran-2-yl 9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-prostenoate (Example 123) in glacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45°C. for 3.5 hours. The solution is diluted with water and extracted with ether. The extract is washed successively with water and saturated sodium chloride solution and dried over magnesium sulfate. The solvents are removed at reduced pressure. Column chromatography of the residue on acid-washed silica gel gives the title compounds as a pair of epimeric substances which are purified separately by partition chromatography.

The fast-running epimer (15-epi-d,1-prostaglandin E₁) is obtained as an oil, ν max. 1735 (ketone carbonyl group), 1710 (acid carbonyl group), and 967 cm.sup.⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.68 (multiplet, vinyl hydrogens) and 4.11 δ(multiplet, carbinolic hydrogens).

The slow-running epimer (d,1-prostaglandin E₁) is recrystallized from ethyl acetate-petroleum ether to give white crystals, m.p. 100°-105°C., ν max. (KBr) 1725 (ketone carbonyl group), 1700 (acid carbonyl group), and 970 cm.sup.⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.67 (multiplet, vinyl hydrogens) and 4.12 (multiplet, carbinolic hydrogens).

EXAMPLES 125 to 139 In accordance with the method described in Example 119, the various 3-hydroxy-1-alkynes listed in the table below are converted to the corresponding 3-triphenylmethoxy-1-alkynes by treatment with triphenylmethyl bromide.

                  TABLE                                                            ______________________________________                                         125  1-heptyn-3-ol   3-triphenylmethoxyheptyne-1                               126  1-hexyn-3-ol    3-triphenylmethoxy-hexyne-1                               127  1-pentyn-3-ol   3-triphenylmethoxy-pentyne-1                              128  1-nonyne-3-ol.sup.a                                                                            3-triphenylmethoxy-nonyne-1                               129  1-decyne-3-ol.sup.b                                                                            3-triphenylmethoxy-decyne-1                               130  4-ethyl-1-octyne-3-ol                                                                          3-triphenylmethoxy-4-ethyl-                                                    octyne-1                                                  131  4-ethyl-1-hexyne-3-ol                                                                          3-triphenylmethoxy-4-ethyl-                                                    hexyne-1                                                  132  4-methyl-1-heptyne-3-ol                                                                        3-triphenylmethoxy-4-methyl-                                                   heptyne-1                                                 133  4-methyl-1-pentyne-3-ol                                                                        3-triphenylmethoxy-4-methyl-                                                   pentyne-1                                                 134  7-methyl-6-en-1-octyne-                                                                        3-triphenylmethoxy-7-methyl-                                   3-ol.sup.c      6-en-octyne-1                                             135  6,7-dimethyl-6-en-1-                                                                           3-triphenylmethoxy-6,7-                                        octyne-3-ol.sup.c                                                                              dimethyl-6-en-octyne-1                                    136  7-isobutyl-6-en-1-                                                                             3-triphenylmethoxy-7-isobutyl-                                 octyne-3-ol.sup.c                                                                              6-en-octyne-1                                             137  5-en-1-hexyne-3-ol.sup.d                                                                       3-triphenylmethoxy-5-en-                                                       hexyne-1                                                  138  5,9-dimethyl-9-en-1-                                                                           3-triphenylmethoxy-5,9-                                        decyne-3-ol.sup.e                                                                              dimethyl-9-en-decyne-1                                    139  cis-5-en-1-octyne-3-                                                                           3-triphenylmethoxy-cis-5-en-                                   ol.sup.f        octyne-1                                                  ______________________________________                                         References:                                                                    a.  M. Bertrand, Bull. Soc. Chim. France, 461 (1956).                          b.  F. Bohlmann and D. Ratz, Chem. Ber., 90, 2265 (1957).                      c.  U.S. Pat. No. 3,452,105 (June 24, 1969); Chem. Abs., 71,                       60678 (1969).                                                              d.  A. Viola and J. H. MacMillan, Jour. Amer. Chem. Soc.,                          92, 2404 (1970).                                                           e.  Sequin, Bull. Soc. Chim. France, 12, 948 (1945).                           f.  J. Fried et al., Jour. Amer. Chem. Soc., 94, 4342                              (1972).                                                                    ______________________________________                                    

EXAMPLES 140-256

Treatment of the cycloalkenone designated in the table below with the alanate [lithium diisobutyl-methyl-(3-triphenylmethoxy-1-trans-alkenyl)-alanate] prepared by treatment of the listed 3-triphenylmethoxy-1-alkyne with diisobutyl aluminum hydride followed with methyl lithium, all by the procedure described in Example 120, is productive 9-oxo-15-triphenylmethoxy-13-trans-8-ξ -prostenoates of the table.

                                      Table 3                                      __________________________________________________________________________                       Starting 3-triphenyl-                                                                       Product                                              Starting Cycloalkenone                                                                      methoxy-1-alkyne of                                                                         Alkyl 9-oxo-15-triphenylmethoxy-13-trans-       Example                                                                             of Example   Example                                                      8ξ-prostenoate                                                              __________________________________________________________________________     140  14           119          ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri-                                     9                                                                              nor-13-trans-8ξ-prostenoate                  141  23           119          ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis-                                     .                                                                              homo-13-trans-8ξ-prostenoate                 142  31           119          ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-13-                                    8                                                                              trans-8ξ-prostenoate                         143  41           119          ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy                                    l-                                                                             13-trans-8ξ-prostenoate                      144  46           119          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-13-                                      trans-8ξ-prostenoate                         145  53           119          ethyl 9-oxo-15-triphenylmethoxy-7-nor-13-                                      trans-8ξ-prostenoate                         146  70           119          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-13                                    -                                                                              trans-8ξ-prostenoate                         147  74           119          ethyl 9-oxo-15-triphenylmethoxy-7a-homo-13-                                    O                                                                              13-trans-8ξ-prostenoate                      148  79           119          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-13                                    -                                                                              trans-8ξ-prostenoate                         149  99           119          ethyl 9-oxo-15-triphenylmethoxy-2-methyl-13                                    -                                                                              trans-8ξ-prostenaoate                        150  111          119          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-13                                    -                                                                              trans-8ξ-prostenoate                         151  112          119          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,                                    -                                                                              6,7-trinor-13-trans-8ξ-prostenoate           152  113          119          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-                                    nor-13-trans-8ξ-prostenoate                  153  114          119          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                    N                                                                              homo-13-trans-8ξ-prostenoate                 154  118          119          ethyl 9-oxo-15-triphenylmethoxy-3-thia-13-                                     O                                                                              13-trans-8ξ-prostenoate                      155  81           119          butyl 9-oxo-15-triphenylmethoxy-13-trans-8.                                    xi.-                                                                           prostenoate                                     156  82           119          isopropyl 9-oxo-15-triphenylmethoxy-13-tran                                    s-                                                                             8ξ-prostenoate                               157  83           119          methyl 9-oxo-15-triphenylmethoxy-13-trans-8                                    ξ-                                                                          prostenoate                                     158  84           119          n-decyl 9-oxo-15-triphenylmethoxy-13-trans-                                    8ξ-prostenoate                               159  900          119          methyl 9-oxo-15-triphenylmethoxy-5-cis,13-                                     trans-8ξ-prostadienoate                      160  13           125          ethyl 9-oxo-15-triphenylmethoxy-20-nor-13-                                     N                                                                              trans-8ξ-prostenoate                         161  13           128          ethyl 9-oxo-15-triphenylmethoxy-20-methyl-                                     O                                                                              13-trans-8ξ-prostenoate                      162  13           130          ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-13                                    -                                                                              trans-8ξ-prostenoate                         163  13           132          ethyl 9-oxo-15-triphenylmethoxy-16-methyl-2                                    0-                                                                             nor-13-trans-8ξ-prostenoate                  164  13           134          ethyl 9-oxo-15-triphenylmethoxy-19-methyl-1                                    3-                                                                             trans,18-8ξ-prostadienoate                   165  13           135          ethyl 9-oxo-15-triphenylmethoxy-18,19-di-                                      methyl-13-trans,18-8ξ-prostadienoate         166  13           139          ethyl 9-oxo-15-triphenylmethoxy-8ξ-13-tr                                    ans,                                                                           17-cis-prostadienoate                           167  14           139          ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trino                                    r-                                                                             8ξ-13-trans,17-cis-prostadienoate            168  15           139          ethyl 9-oxo-15-triphenylmethoxy-6,7-dinor-8                                    ξ-                                                                          13-trans,17-cis-prostadienoate                  169  23           139          ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bisho                                    mo-                                                                            8ξ-13-trans,17-cis-prostadienoate            170  31           139          ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-8.x                                    i.-13-                                                                         trans,17-cis-prostadienoate                     171  41           139          ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy                                    l-                                                                             8ξ-13-trans,17-cis-prostadienoate            172  46           139          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-8ξ                                    -13-                                                                           trans,17-cis-prostadienoate                     173  53           139          ethyl 9-oxo-15-triphenylmethoxy-7-nor-8ξ                                    -13-                                                                           trans,17-cis-prostadienoate                     174  70           139          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-8.                                    xi.-13-                                                                        trans,17-cis-prostadienoate                     175  74           139          ethyl 9-oxo-15-triphenylmethoxy-7a-homo-8.x                                    i.-13-                                                                         trans,17-cis-prostadienoate                     176  79           139          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-8.                                    xi.-13-                                                                        trans,17-cis-prostadienoate                     177  99           139          ethyl 9-oxo-15-triphenylmethoxy-2-methyl-8.                                    xi.-13-                                                                        trans,17-cis-prostadienoate                     178  111          139          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-8.                                    xi.-13-                                                                        trans,17-cis-prostadienoate                     179  112          139          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,                                    6,7-                                                                           trinor-13-trans, 17-cis-prostadienoate          180  113          139          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-                                    nor-                                                                           8ξ-13-trans,17-cis-prostadienoate            181  114          139          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bish                                    omo-                                                                           8ξ-13-trans,17-cis-prostadienoate            182  118          139          ethyl 9-oxo-15-triphenylmethoxy-3-thia-8.xi                                    .-13-                                                                          trans,17-cis-prostadienoate                     183  81           139          butyl 9-oxo-15-triphenylmethoxy-8ξ-13-tr                                    ans,17-                                                                        cis-prostadienoate                              184  82           139          isopropyl 9-oxo-15-triphenylmethoxy-8ξ-1                                    3-trans,                                                                       cis-prostadienoate                              185  83           139          methyl 9-oxo-15-triphenylmethoxy-8ξ-13-t                                    rans,                                                                          17-cis-prostadienoate                           186  84           139          n-decyl 9-oxo-15-triphenylmethoxy-8ξ-13-                                    trans,17-                                                                      cis-prostadienoate                              187  14           136          ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trino                                    r-19-                                                                          isobutyl-8ξ-13-trans,18-prostadienoate       188  14           137          ethyl 9-oxo-15-triphenylmethoxy-5,6,7,19,20                                    -penta-                                                                        nor-8ξ-13-trans-17,prostadienoate            189  13           137          ethyl 9-oxo-15-triphenylmethoxy-19,20-dinor                                    -8ξ-13-                                                                     trans,18-prostadienoate                         190  13           138          ethyl 9-oxo-15-triphenylmethoxy-17-methyl-2                                    0-iso-                                                                         propenyl-8ξ-trans-prostenoate                191  15           131          ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-6,                                    7,19,                                                                          20-tetranor-8ξ-13-trans-prostenoate          192  15           135          ethyl 9-oxo-15-triphenylmethoxy-18,19-dimet                                    hyl-6,                                                                         7-dinor-8ξ-13-trans,18-prostadienate         193  23           130          ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-7a                                    ,7b-                                                                           bishomo-8ξ-13-trans-prostenoate              194  23           134          ethyl 9-oxo-15-triphenylmethoxy-19-methyl-7                                    a,7b-                                                                          bishomo-8ξ-13-trans,18-prostadienoate        195  31           126          ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-19,                                    20-                                                                            dinor-8ξ-13-trans-prostenoate                196  31           129          ethyl 9-oxo-15-triphenylmethoxy-2,20-diethy                                    l-                                              8ξ-13-trans-prostenoate                                                     197  31           132          ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-16-                                    methyl-8ξ-20-nor-13-trans-prostenoate        198  31           135          ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-18,                                    19-dimethyl-8ξ-13-trans,18-prostadienoat                                    e                                               199  41           127          ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy                                    l-                                                                             18,19,20-trinor-8ξ-13-trans-prostenoate                                     O                                               200  41           128          ethyl 9-oxo-15-triphenylmethoxy-3,3,20-tri-                                    methyl-8ξ-13-trans-prostenoate               201  41           132          ethyl 9-oxo-15-triphenylmethoxy-3,3,16-tri-                                    methyl-20-nor-8ξ-13-trans-prostenoate        202  41           136          ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy                                    l-                                                                             19-isobutyl-8ξ-13-trans,18-prostadienoat                                    e                                               203  41           137          ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethy                                    l-                                                                             19,20-dinor-8ξ-13-trans,17-prostadienoat                                    e                                               204  46           125          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-no                                    r-                                                                             8ξ-13-trans-prostenoate                      205  46           128          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-                                      methyl-8ξ-13-trans-prostenoate               206  46           130          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                      ethyl-8ξ-13-trans-prostenoate                207  46           132          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                      methyl-20-nor-8ξ-13-trans-prostenoate        208  46           137          ethyl 9-oxo-15-triphenylmethoxy-3-oxa-19,20                                    -                                                                              dinor-8ξ-13-trans,17-prostadienoate          209  53           137          ethyl 9-oxo-15-triphenylmethoxy-7,19,20-tri                                    nor-8ξ-13-trans,17-prostadienoate            210  53           135          ethyl 9-oxo-15-triphenylmethoxy-7-nor-18,19                                    -                                                                              dimethyl-8ξ-13-trans,18-prostadienoate       211  53           133          ethyl 9-oxo-15-triphenylmethoxy-7,18,19,20-                                    tetranor-16-methyl-8ξ-13-trans-prostenoa                                    te                                              212  70           125          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20                                    -                                                                              nor-8ξ-13-trans-prostenoate                  213  70           129          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20                                    -                                                                              ethyl-8ξ-13-trans-prostenoate                214  70           131          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16                                    -                                                                              ethyl-19,20-dinor-8ξ-13-trans-prostenoat                                    e                                               215  70           132          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16                                    -                                                                              methyl-20-nor-8ξ-13-trans-prostenoate        216  70           134          ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-19                                    -                                                                              methyl-8ξ-13-trans,18-prostadienoate         217  74           135          ethyl 9-oxo-15-triphenylmethoxy-7a-homo-18,                                    19-                                                                            dimethyl-8ξ-13-trans,18-prostadienoate       218  74           137          ethyl 9-oxo-15-triphenylmethoxy-7a-homo-19,                                    20-                                                                            dinor-8ξ-13-trans,17-prostadienoate          219  79           125          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20                                    -                                                                              nor-8ξ-13-trans-prostenoate                  220  79           129          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20                                    -                                                                              ethyl-8ξ-13-trans-prostenoate                221  79           130          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16                                    -                                                                              ethyl-8ξ-13-trans-prostenoate                222  79           133          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16                                    -                                                                              methyl-18,19,20-trinor-8ξ-trans-prosteno                                    ate                                             223  79           135          ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-18                                    ,                                               19,-dimethyl-8ξ-13-trans,18-prostadienoate                                  224  99           125          ethyl 9-oxo-15-triphenylmethoxy-2-methyl-20                                    -                                                                              nor-8ξ-13-trans-prostenoate                  225  99           128          ethyl 9-oxo-15-triphenylmethoxy-2,20-dimeth                                    yl-                                                                            8ξ-13-trans-prostenoate                      226  99           131          ethyl 9-oxo-15-triphenylmethoxy-2-methyl-16                                    -                                                                              ethyl-19,20-dinor-8ξ-13-trans-prostenoat                                    e                                               227  99           134          ethyl 9-oxo-15-triphenylmethoxy-2,19-dimeth                                    yl-                                                                            8ξ-13-trans,18-prostadienoate                228  99           137          ethyl 9-oxo-15-triphenylmethoxy-2-methyl-19                                    ,                                                                              20-dinor-8ξ-13-trans,17-prostadienoate       229  111          125          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20                                    -                                                                              nor-8ξ-13-trans-prostenoate                  230  111          128          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20                                    -                                                                              methyl-8ξ-13-trans-prostenoate               231  111          130          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-16                                    -                                                                              ethyl-8ξ-13-trans-prostenoate                232  111          135          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-18                                    ,                                                                              19-dimethyl-8ξ-13-trans,18-prostadienoat                                    e                                               233  111          137          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19                                    ,                                                                              20-dinor-8ξ-13-trans,17-prostadienoate       234  112          129          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,                                    6,                                                                             7-trinor-20-ethyl-8ξ-13-trans-prostenoat                                    e                                               235  112          132          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,                                    6,                                                                             7,20-tetranor-16-methyl-8ξ-13-trans-pros                                    t-                                                                             enoate                                          236  112          136          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,                                    6,7-                                                                           trinor-19-isobutyl-8ξ-13-trans,18-prosta                                    dienoate                                        237  113          128          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20                                    -                                                                              methyl-8ξ-13-trans-prostenoate               238  113          134          ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19                                    -                                                                              methyl-8ξ-13-trans,18-prostadienoate         239  114          125          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                    homo-20-nor-8ξ-13-trans-prostenoate          240  114          129          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                    homo-20-ethyl-8ξ-13-trans-prostenoate        241  114          132          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                    J                                                                              homo-16-methyl-20-nor-8ξ-13-trans-proste                                    noate                                           242  114          134          ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                    n                                                                              homo-19-methyl-8ξ-13-trans,18-prostadien                                    oate                                            243  118          125          ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-n                                    or-                                                                            8ξ-13-trans-prostenoate                      244  118          128          ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-m                                    ethyl-                                                                         8ξ-13-trans-prostenoate                      245  118          130          ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-                                     e                                                                              8ξ-13-trans-prostenoate                      246  118          133          ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-                                     b                                                                              methyl-18,19,20-trinor-8ξ-13-trans-prost                                    enoate                                          247  118          134          ethyl 9-oxo-15-triphenylmethoxy-3-thia-19-m                                    ethyl-                                                                         8ξ-13-trans,18-prostadienoate                248  118          137          ethyl 9-oxo-15-triphenylmethoxy-3-thia-19,2                                    0-                                                                             dinor-8ξ-13-trans,17-prostadienoate          249  900          125          methyl 9-oxo-15-triphenylmethoxy-20-nor-8.x                                    i.-5-                                                                          cis,13-trans-prostadienoate                     250  900          128          methyl 9-oxo-15-triphenylmethoxy-20-methyl-                                    8ξ-5-                                                                       cis,13-trans-prostadienoate                     251  900          130          methyl 9-oxo-15-triphenylmethoxy-16-ethyl-8                                    ξ-5-                                                                        cis,13-trans-prostadienoate                     252  900          132          methyl 9-oxo-15-triphenylmethoxy-16-methyl-                                    20-                                                                            nor-8ξ-5-cis,13-trans-prostadienoate         253  900          134          methyl 9-oxo-15-triphenylmethoxy-19-methyl-                                    8ξ-5-                                                                       cis,13-trans,18-prostatrienoate                 254  900          135          methyl 9-oxo-15-triphenylmethoxy-18,19-dime                                    thyl-                                                                          8ξ-5-cis,13-trans,18-prostatrienoate         255  900          137          methyl 9-oxo-15-triphenylmethoxy-19,20-dino                                    r-8ξ-                                                                       5-cis,13-trans,17-prostatrienoate               256  900          139          methyl 9-oxo-15-triphenylmethoxy-8ξ-5-ci                                    s,13-                                                                          trans,17-cis-prostatrienoate                    __________________________________________________________________________

EXAMPLE 257 Preparation of ethyl 9α/β,15-dihydroxy-13-trans-prostenoate

A solution containing 3 g. of ethyl 9-oxo-15-hydroxy-13-trans-prostenoate (Example 121) in 120 ml. of absolute alcohol containing 115 mg. of sodium borohydride is stirred at ambient temperature for 18 hours. The solution is poured into 300 ml. of saturated sodium chloride solution and the oily precipitate is extracted with ether. The ether is washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give subject product as an oil; λ max. 2195, 5178, 8.45 μ; the product is a mixture of 9α- and 9β-hydroxy derivatives.

EXAMPLES 258-374 Treatment of the designated 9-oxo-15-triphenylmethoxy derivatives listed in the table below, with glacial acetic acid-tetrahydropyran-water (4:2:1) in the manner described in Example 121 is productive of the corresponding 15-hydroxy derivatives of the table. This acid treatment also ensures a trans-relationship between the two side-chains attached to C₈ and C₁₂.

                  TABLE 4                                                          ______________________________________                                         Ex-    Starting 15-tri-                                                                             Product Alkyl 9-oxo-                                      ample  phenylmethoxy                                                           15-hydroxy-13-trans-                                                                  derivative of                                                           prostenoates                                                                          Example                                                                 ______________________________________                                         258    140           Ethyl 9-oxo-15-hydroxy-5,6,7-trinor-13-trans-prosteno                          ate                                                       259    141           Ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-13-trans-prosten                          oate                                                      260    142           Ethyl 9-oxo-15-hydroxy-2-ethyl-13-trans-prostenoate       261    143           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prosteno                          ate                                                       262    144           Ethyl 9-oxo-15-hydroxy-3-oxa-13-trans-prostenoate         263    145           Ethyl 9-oxo-15-hydroxy-7-nor-13-trans-prostenoate         264    146           Ethyl 9-oxo-15-hydroxy-2-fluoro-13-trans-prostenoate                           N                                                         265    147           Ethyl 9-oxo-15-hydroxy-7a-homo-13-trans-prostenoate       266    148           Ethyl 9-oxo-15-hydroxy-2-phenyl-13-trans-prostenoate                           O                                                         267    149           Ethyl 9-oxo-15-hydroxy-2-methyl-13-trans-prostenoate                           y                                                         268    150           Ethyl 9-oxo-15-hydroxy-10a-homo-13-trans-prostenoate                           0                                                         269    151           Ethyl 9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-13-trans                          -prostenoate                                              270    152           Ethyl 9-oxo-15-hydroxy-10a-homo-7-nor-13-trans-proste                          noate                                                     271    153           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-13-trans-proste                          noate                                                     272    154           Ethyl 9-oxo-15-hydroxy-3-thia-13-trans-prostenoate        273    155           Butyl 9-oxo-15-hydroxy-13-trans-prostenoate               274    156           Isopropyl 9-oxo-15-hydroxy-13-trans-prostenoate           275    157           Methyl 9-oxo-15-hydroxy-13-trans-prostenoate              276    158           n-decyl 9-oxo-15-hydroxy-13-trans-prostenoate             277    159           Methyl 9-oxo-15-hydroxy-5-cis,-13-trans-prostadienoat                          e                                                         278    160           Ethyl 9-oxo-15-hydroxy-20-nor-13-trans-prostenoate        279    161           Ethyl 9-oxo-15-hydroxy-20-methyl-13-trans-prostenoate                          0                                                         280    162           Ethyl 9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoate                           6                                                         281    163           Ethyl 9-oxo-15-hydroxy-16-methyl-20-nor-13-trans-pros                          tenoate                                                   282    164           Ethyl 9-oxo-15-hydroxy-19-methyl-13-trans,18-prostadi                          enoate                                                    283    165           Ethyl 9-oxo-15-hydroxy-18,19-dimethyl-13-trans,18-pro                          stadienoate                                               284    166           Ethyl 9-oxo-15-hydroxy-13-trans,17-cis-prostadienoate                          0                                                         285    167           Ethyl 9-oxo-15-hydroxy-5,6,7-trinor-13-trans,17-cis-p                          rostadienoate                                             286    168           Ethyl 9-oxo-15-hydroxy-6,7-dinor-13-trans-17-cis-pros                          tadienoate                                                287    169           Ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-13-trans,17-cis-                          prostadienoate                                            288    170           Ethyl 9-oxo-15-hydroxy-2-ethyl-13-trans,17-cis-prosta                          dienoate                                                  289    171           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-13-trans,17-cis-p                          rostadienoate                                             290    172           Ethyl 9-oxo-15-hydroxy-3-oxa-13-trans,17-cis-prostadi                          enoate                                                    291    173           Ethyl 9-oxo-15-hydroxy-7-nor-13-trans,17-cis-prostadi                          enoate                                                    292    174           Ethyl 9-oxo-15-hydroxy-2-fluoro-13-trans,17-cis-prost                          adienoate                                                 293    175           Ethyl 9-oxo-15-hydroxy-7a-homo-13-trans,17-cis-prosta                          dienoate                                                  294    176           Ethyl 9-oxo-15-hydroxy-2-phenyl-13-trans,17-cis-prost                          adienoate                                                 295    177           Ethyl 9-oxo-15-hydroxy-2-methyl-13-trans,17-cis-prost                          adienoate                                                 296    178           Ethyl 9-oxo-15-hydroxy-10a-homo-13-trans,17-cis-prost                          adienoate                                                 297    179           Ethyl 9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-13-trans                          ,17-cis-prostadienoate                                    298    180           Ethyl 9-oxo-15-hydroxy-10a-homo-7-nor-13-trans,17-cis                          -prostadienoate                                           299    181           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-13-trans,17-cis                          -prostadienoate                                           300    182           Ethyl 9-oxo-15-hydroxy-3-thia-13-trans,17-cis-prostad                          ienoate                                                   301    183           Butyl 9-oxo-15-hydroxy-13-trans,17-cis-prostadienoate                          N                                                         302    184           Isopropyl 9-oxo-15-hydroxy-13-trans,17-cis-prostadien                          oate                                                      303    185           Methyl 9-oxo-15-hydroxy-13-trans,17-cis-prostadienoat                          e                                                         304    186           n-decyl 9-oxo-15-hydroxy-13-trans,17-cis-prostadienoa                          te                                                        305    187           Ethyl 9-oxo-15-hydroxy-5,6,7-trinor-19-isobutyl-13-tr                          ans,18-prostadienoate                                     306    188           Ethyl 9-oxo-15-hydroxy-5,6,7,19,20-pentanor-13-trans,                          17-prostadienoate                                         307    189           Ethyl 9-oxo-15-hydroxy-19,20-dinor-13-trans,18-prosta                          dienoate                                                  308    190           Ethyl 9-oxo-15-hydroxy-17-methyl-20-isopropenyl-13-tr                          ans-prostadienoate                                        309    191           Ethyl 9-oxo-15-hydroxy-16-ethyl-6,7,19,20-tetranor-13                          -trans-prostenoate                                        310    192           Ethyl 9-oxo-15-hydroxy-18,19-dimethyl-6,7-dinor-13-tr                          ans,18-prostadienoate                                     311    193           Ethyl 9-oxo-15-hydroxy-16-ethyl-7a,7b-bishomo-13-tran                          s-prostenoate                                             312    194           Ethyl 9-oxo-15-hydroxy-19-methyl-7a,7b-bishomo-13-tra                          ns,18-prostadienoate                                      313    195           Ethyl 9-oxo-15-hydroxy-2-ethyl-19,20-dinor-13-trans-p                          rostenoate                                                314    196           Ethyl 9-oxo-15-hydroxy-2,20-diethyl-13-trans-prosteno                          ate                                                       315    197           Ethyl 9-oxo-15-hydroxy-2-ethyl-16-methyl-20-nor-trans                          -prostenoate                                              316    198           Ethyl 9-oxo-15-hydroxy-2-ethyl-18,19-dimethyl-13-tran                          s,18-prostadienoate                                       317    199           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-18,19,20-trinor-1                          3-trans-prostenoate                                       318    200           Ethyl 9-oxo-15-hydroxy-3,3,20-trimethyl-13-trans-pros                          tenoate                                                   319    201           Ethyl 9-oxo-15-hydroxy-3,3,16-trimethyl-20-nor-13-tra                          ns-prostanoate                                            320    202           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-19-isobutyl-13-tr                          ans,18-prostadienoate                                     321    203           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-19,20-dinor-13-tr                          ans,17-prostadienoate                                     322    204           Ethyl 9-oxo-15-hydroxy-3-oxa-20-nor-13-trans-prosteno                          ate                                                       323    205           Ethyl 9-oxo-15-hydroxy-3-oxa-20-methyl-13-trans-prost                          enoate                                                    324    206           Ethyl 9-oxo-15-hydroxy-3-oxa-16-ethyl-13-trans-proste                          noate                                                     325    207           Ethyl 9-oxo-15-hydroxy-3-oxa-16-methyl-20-nor-13-tran                          s-prostenoate                                             326    208           Ethyl 9-oxo-15-hydroxy-3-oxa-19,20-dinor-13-trans,17-                          prostadienoate                                            327    209           Ethyl 9-oxo-15-hydroxy-7,19,20-trinor-13-trans,17-pro                          stadienoate                                               328    210           Ethyl 9-oxo-15-hydroxy-7-nor-18,19-dimethyl-13-trans,                          18-prostadienoate                                         329    211           Ethyl 9-oxo-15-hydroxy-7,18,19,20-tetranor-16-methyl-                          13-trans-prostenoate                                      330    212           Ethyl 9-oxo-15-hydroxy-2-fluoro-20-nor-13-trans-prost                          enoate                                                    331    213           Ethyl 9-oxo-15-hydroxy-2-fluoro-20-ethyl-13-trans-pro                          stenoate                                                  332    214           Ethyl 9-oxo-15-hydroxy-2-fluoro-16-ethyl-19,20-dinor-                          13-trans-prostenoate                                      333    215           Ethyl 9-oxo-15-hydroxy-2-fluoro-16-methyl-20-nor-13-t                          rans-prostenoate-prostenoate                              334    216           Ethyl 9-oxo-15-hydroxy-2-fluoro-19-methyl-13-trans,18                          -prostadienoate                                           335    217           Ethyl 9-oxo-15-hydroxy-7a-homo-18,19-dimethyl-13-tran                          s,18-prostadienoate                                       336    218           Ethyl 9-oxo-15-hydroxy-7a-homo-19,20-dinor-13-trans,1                          7-prostadienoate                                          337    219           Ethyl 9-oxo-15-hydroxy-2-phenyl-20-nor-13-trans-prost                          enoate                                                    338    220           Ethyl 9-oxo-15-hydroxy-2-phenyl-20-ethyl-13-trans-pro                          stenoate                                                  339    221           Ethyl 9-oxo-15-hydroxy-2-phenyl-16-ethyl-13-trans-pro                          stenoate                                                  340    222           Ethyl 9-oxo-15-hydroxy-2-phenyl-16-methyl-18,19,20-tr                          inor-13-trans-prostenoate                                 341    223           Ethyl 9-oxo-15-hydroxy-2-phenyl-18,19-dimethyl-13-tra                          ns,18-prostadienoate                                      342    224           Ethyl 9-oxo-15-hydroxy-2-methyl-20-nor-13-trans-prost                          enoate                                                    343    225           Ethyl 9-oxo-15-hydroxy-2,20-dimethyl-13-trans-prosten                          oate                                                      344    226           Ethyl 9-oxo-15-hydroxy-2-methyl-16-ethyl-19,20-dinor-                          13-trans-prostenoate                                      345    227           Ethyl 9-oxo-15-hydroxy-2,19-dimethyl-13-trans,18-pros                          tadienoate                                                346    228           Ethyl 9-oxo-15-hydroxy-2-methyl-19,20-dinor-13-trans,                          17-prostadienoate                                         347    229           Ethyl 9-oxo-15-hydroxy-10a-homo-20-nor-13-trans-prost                          enoate                                                    348    230           Ethyl 9-oxo-15-hydroxy-10a-homo-20-methyl-13-trans-pr                          ostenoate                                                 349    231           Ethyl 9-oxo-15-hydroxy-10a-homo-16-ethyl-13-trans-pro                          stenoate                                                  350    232           Ethyl 9-oxo-15-hydroxy-10a-homo-18,19-dimethyl-13-tra                          ns,18-prostadienoate                                      351    233           Ethyl 9-oxo-15-hydroxy-10a-homo-19,20-dinor-13-trans,                          17-prostadienoate                                         352    234           Ethyl 9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-20-ethyl                          -13-trans-prostenoate                                     353    235           Ethyl 9-oxo-15-hydroxy-10a-homo-5,6,7,20-tetranor-16-                          methyl-13-trans-prostenoate                               354    236           Ethyl 9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-19-isobu                          tyl-13-trans,18-prostadienoate                            355    237           Ethyl 9-oxo-15-hydroxy-10a-homo-20-methyl-13-trans-pr                          ostenoate                                                 356    238           Ethyl 9-oxo-15-hydroxy-10a-homo-19-methyl-13-trans,18                          -prostadienoate                                           357    239           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-20-nor-13-trans                          -prostenoate                                              358    240           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-20-ethyl-13-tra                          ns-prostenoate                                            359    241           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-16-methyl-20-no                          r-13-trans-prostenoate                                    360    242           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-19-methyl-13-tr                          ans,18-prostadienoate                                     361    243           Ethyl 9-oxo-15-hydroxy-3-thia-20-nor-13-trans-prosten                          oate                                                      362    244           Ethyl 9-oxo-15-hydroxy-3-thia-20-methyl-13-trans-pros                          tenoate                                                   363    245           Ethyl 9-oxo-15-hydroxy-3-thia-16-ethyl-13-trans-prost                          enoate                                                    364    246           Ethyl 9-oxo-15-hydroxy-3-thia-16-methyl-18,19,20-trin                          or-13-trans-prostenoate                                   365    247           Ethyl 9-oxo-15-hydroxy-3-thia-19-methyl-13-trans,18-p                          rostadienoate                                             366    248           Ethyl 9-oxo-15-hydroxy-3-thia-19,20-dinor-13-trans,17                          -prostadienoate                                           367    249           Methyl 9-oxo-15-hydroxy-20-nor-5-cis,13-trans-prostad                          ienoate                                                   368    250           Methyl 9-oxo-15-hydroxy-20-methyl-5-cis,13-trans-pros                          tadienoate                                                369    251           Methyl 9-oxo-15-hydroxy-16-ethyl-5-cis,13-trans-prost                          adienoate                                                 370    252           Methyl 9-oxo-15-hydroxy-16-methyl-20-nor-5-cis,13-tra                          ns-prostadienoate                                         371    253           Methyl 9-oxo-15-hydroxy-19-methyl-5-cis,13-trans,18-p                          rostatrienoate                                            372    254           Methyl 9-oxo-15-hydroxy-18,19-dimethyl-5-cis,13-trans                          ,18-prostatrienoate                                       373    255           Methyl 9-oxo-15-hydroxy-19,20-dinor-5-cis,13-trans,17                          -prostatrienoate                                          374    256           Methyl 9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostat                          rienoate                                                  ______________________________________                                    

EXAMPLES 375-491

Saponification of the alkyl esters designated in the following table by the method described in Example 122 is productive of the prostenoic acids of the table.

                  Table 5                                                          ______________________________________                                               Starting alkyl 9-                                                                             Product                                                   Ex-                                                                            oxo-prostenoate                                                                      9-Oxo-15-hydroxy-13-                                                     ample of example                                                               trans-prostenoic acid                                                          ______________________________________                                         375   258            9-oxo-15-hydroxy-5,6,7-trinor-13-trans-prostenoic                              acid                                                      376   259            9-oxo-15-hydroxy-7a,7b-bishomo-13-trans-prostenoic                             acid                                                      377   260            9-oxo-15-hydroxy-2-ethyl-13-trans-prostenoic acid         378   261            9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic                              acid                                                      379   262            9-oxo-15-hydroxy-3-oxa-13-trans-prostenoic acid           380   263            9-oxo-15-hydroxy-7-nor-13-trans-prostenoic acid           381   264            9-oxo-15-hydroxy-2-fluoro-13-trans-prostenoic acid        382   265            9-oxo-15-hydroxy-7a-homo-13-trans-prostenoic acid         383   266            9-oxo-15-hydroxy-2-phenyl-13-trans-prostenoic acid        384   267            9-oxo-15-hydroxy-2-methyl-13-trans-prostenoic acid        385   268            9-oxo-15-hydroxy-10a-homo-13-trans-prostenoic acid        386   269            9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-13-trans-prost                          enoic acid                                                387   270            9-oxo-15-hydroxy-10a-homo-7-nor-13-trans-prostenoic                            acid                                                      388   271            9-oxo-15-hydroxy-7a,10a-bishomo-13-trans-prostenoic                            acid                                                      389   272            9-oxo-15-hydroxy-3-thia-13-trans-prostenoic acid          390   273            9-oxo-15-hydroxy-13-trans-prostenoic acid                 391   274            9-oxo-15-hydroxy-13-trans-prostenoic acid                 392   275            9-oxo-15-hydroxy-13-trans-prostenoic acid                 393   276            9-oxo-15-hydroxy-13-trans-prostenoic acid                 394   277            9-oxo-15-hydroxy-5-cis,13-trans-prostadienoic acid        395   278            9-oxo-15-hydroxy-20-nor-13-trans-prostenoic acid          396   279            9-oxo-15-hydroxy-20-methyl-13-trans-prostenoic acid       397   280            9-oxo-15-hydroxy-16-ethyl-13-trans-prostenoic acid        398   281            9-oxo-15-hydroxy-16-methyl-20-nor-13-trans-prostenoic                           acid                                                     399   282            9-oxo-15-hydroxy-19-methyl-13-trans,18-prostadienoic                           acid                                                      400   283            9-oxo-15-hydroxy-18,19-dimethyl-13-trans,18-prostadie                          noic acid                                                 401   284            9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid       402   285            9-oxo-15-hydroxy-5,6,7-trinor-13-trans,17-cis-prostad                          ienoic acid                                               403   286            9-oxo-15-hydroxy-6,7-dinor-13-trans,17-cis-prostadien                          oic acid                                                  404   287            9-oxo-15-hydroxy-7a,7b-bishomo-13-trans,17-cis-prosta                          dienoic acid                                              405   288            9-oxo-15-hydroxy-2-ethyl-13-trans,17-cis-prostadienoi                          c acid                                                    406   289            9-oxo-15-hydroxy-3,3-dimethyl-13-trans,17-cis-prostad                          ienoic acid                                               407   290            9-oxo-15-hydroxy-3-oxa-13-trans,17-cis-prostadienoic                           acid                                                      408   291            9-oxo-15-hydroxy-7-nor-13-trans,17-cis-prostadienoic                           acid                                                      409   292            9-oxo-15-hydroxy-2-fluoro-13-trans,17-cis-prostadieno                          ic acid                                                   410   293            9-oxo-15-hydroxy-7a-homo-13-trans,17-cis-prostadienoi                          c acid                                                    411   294            9-oxo-15-hydroxy-2-phenyl-13-trans,17-cis-prostadieno                          ic acid                                                   412   295            9-oxo-15-hydroxy-2-methyl-13-trans,17-cis-prostadieno                          ic acid                                                   413   296            9-oxo-15-hydroxy-10a-homo-13-trans,17-cis-prostadieno                          ic acid                                                   414   297            9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-13-trans,17-ci                          s-prostadienoic acid                                      415   298            9-oxo-15-hydroxy-10a-homo-7-nor-13-trans,17-cis-prost                          adienoic acid                                             416   299            9-oxo-15-hydroxy-7a,10a-bishomo-13-trans,17-cis-prost                          adienoic acid                                             417   300            9-oxo-15-hydroxy-3-thia-13-trans,17-cis-prostadienoic                           acid                                                     418   301            9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid       419   302            9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid       420   303            9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid       421   304            9-oxo-15-hydroxy-13-trans,17-cis-prostadienoic acid       422   305            9-oxo-15-hydroxy-5,6,7-trinor-19-isobutyl-13-trans,18                          -prostadienoic acid                                       423   306            9-oxo-15-hydroxy-5,6,7,19,20-pentanor-13-trans,17-pro                          stadienoic acid                                           424   307            9-oxo-15-hydroxy-19,20-dinor-13-trans,18-prostadienoi                          c acid                                                    425   308            9-oxo-15-hydroxy-17,-methyl-20-isopropenyl-13-trans-p                          rostenoic acid                                            426   309            9-oxo-15-hydroxy-16-ethyl-6,7,19,20-tetra-nor-13-tran                          s-prostenoic acid                                         427   310            9-oxo-15-hydroxy-18,19-dimethyl-6,7-dinor-13-trans,18                          -prostadienoic acid                                       428   311            9-oxo-15-hydroxy-16-ethyl-7a,7b-bishomo-13-trans-pros                          tenoic acid                                               429   312            9-oxo-15-hydroxy-19-methy-7a,7b-bishomo-13-trans,18-p                          rostadienoic acid                                         430   313            9-oxo-15-hydroxy-2-ethyl-19,20-dinor-13-trans-prosten                          oic acid                                                  431   314            9-oxo-15-hydroxy-2,20-diethyl-13-trans-prostenoic                              acid                                                      432   315            9-oxo-15-hydroxy-2-ethyl-16-methyl-20-nor-13-trans-pr                          ostenoic acid                                             433   316            9-oxo-15-hydroxy-2-ethyl-18,19-dimethyl-13-trans,18-p                          rostadienoic acid                                         434   317            9-oxo-15-hydroxy-3,3-dimethyl-18,19,20-trinor-13-tran                          s-prostenoic acid                                         435   318            9-oxo-15-hydroxy-3,3-20-trimethyl-13-trans-prostenoic                           acid                                                     436   319            9-oxo-15-hydroxy-3,3,16-trimethyl-20-nor-13-trans-pro                          stenoic acid                                              437   320            9-oxo-15-hydroxy-3,3-dimethyl-19-isobutyl-13-trans,18                          -prostadienoic acid                                       438   321            9-oxo-15-hydroxy-3,3-dimethyl-19,20-dinor-13-trans,17                          -prostadienoic acid                                       439   322            9-oxo-15-hydroxy-3-oxa-20-nor-13-trans-prostenoic                              acid                                                      440   323            9-oxo-15-hydroxy-3-oxa-20-methyl-13-trans-prostenoic                           acid                                                      441   324            9-oxo-15-hydroxy-3-oxa-16-ethyl-13-trans-prostenoic                            acid                                                      442   325            9-oxo-15-hydroxy-3-oxa-16-methyl-20-nor-13-trans-pros                          tenoic acid                                               443   326            9-oxo-15-hydroxy-3-oxa-19,20-dinor-13-trans,17-prosta                          dienoic acid                                              444   327            9-oxo-15-hydroxy-7,19,20-trinor-13-trans,17-prostadie                          noic acid                                                 445   328            9-oxo-15-hydroxy-7-nor-18,19-dimethyl-13-trans,18-pro                          stadienoic acid                                           446   329            9-oxo-15-hydroxy-7,18,19,20-tetranor-16-methyl-13-tra                          ns-prostenoic acid                                        447   330            9-oxo-15-hydroxy-2-fluoro-20-nor-13-trans-prostenoic                           acid                                                      448   331            9-oxo-15-hydroxy-2-fluoro-20-ethyl-13-trans-prostenoi                          c acid                                                    449   332            9-oxo-15-hydroxy-2-fluoro-16-ethyl-19,20-dinor-13-tra                          ns-prostenoic acid                                        450   333            9-oxo-15-hydroxy-2-fluoro-16-methyl-20-nor-13-trans-p                          rostenoic acid                                            451   334            9-oxo-15-hydroxy-2-fluoro-19-methyl-13-trans,18-prost                          adienoic acid                                             452   335            9-oxo-15-hydroxy-7a-homo-18,19-dimethyl-13-trans,18-p                          rostadienoic acid                                         453   336            9-oxo-15-hydroxy-7a-homo-19,20-dinor-13-trans,17-pros                          tadienoic acid                                            454   337            9-oxo-15-hydroxy-2-phenyl-20-nor-13-trans-prostenoic                           acid                                                      455   338            9-oxo-15-hydroxy-2-phenyl-20-ethyl-13-trans-prostenoi                          c acid                                                    456   339            9-oxo-15-hydroxy-2-phenyl-16-ethyl-13-trans-prostenoi                          c acid                                                    457   340            9-oxo-15-hydroxy-2-phenyl-16-methyl-18,19,20-trinor-1                          3-trans-prostenoic acid                                   458   341            9-oxo-15-hydroxy-2-phenyl-18,19-dimethyl-13-trans,18-                          prostadienoic acid                                        459   342            9-oxo-15-hydroxy-2-methyl-20-nor-13-trans-prostenoic                           acid                                                      460   343            9-oxo-15-hydroxy-2,20-dimethyl-13-trans-prostenoic                             acid                                                      461   344            9-oxo-15-hydroxy-2-methyl-16-ethyl-19,20-dinor-13-tra                          ns-prostenoic acid                                        462   345            9-oxo-15-hydroxy-2,19-dimethyl-13-trans,18-prostadien                          oic acid                                                  463   346            9-oxo-15-hydroxy-2-methyl-19,20-dinor-13-trans,17-pro                          stadienoic acid                                           464   347            9-oxo-15-hydroxy-10a-homo-20-nor-13-trans-prostenoic                           acid                                                      465   348            9-oxo-15-hydroxy-10a-homo-20-methyl-13-trans-prosteno                          ic acid                                                   466    349           9-oxo-15-hydroxy-10a-homo-16-ethyl-13-trans-prostenoi                          c acid                                                    467   350            9-oxo-15-hydroxy-10a-homo-18,19-dimethyl-13-trans,18-                          prostadienoic acid                                        468   351            9-oxo-15-hydroxy-10a-homo-19,20-dinor-13-trans,17-pro                          stadienoic acid                                           469   352            9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-20-ethyl-13-tr                          ans-prostenoic acid                                       470   353            9-oxo-15-hydroxy-10a-homo-5,6,7,20-tetra-nor-16-methy                          l-13-trans-prostenoic acid                                471   354            9-oxo-15-hydroxy-10a-homo-5,6,7-trinor-19-isobutyl-13                          -trans,18-prostadienoic acid                              472   355            9-oxo-15-hydroxy-10a-homo-20-methyl-13-trans-prosteno                          ic acid                                                   473   356            9-oxo-15-hydroxy-10a-homo-19-methyl-13-trans,18-prost                          adienoic acid                                             474   357            9-oxo-15-hydroxy-7a,10a-bishomo-20-nor-13-trans-prost                          enoic acid                                                475   358            9-oxo-15-hydroxy-7a,10a-bishomo-20-ethyl-13-trans-pro                          stenoic acid                                              476   359            9-oxo-15-hydroxy-7a,10a-bishomo-16-methyl-20-nor-13-t                          rans-prostenoic acid                                      477   360            9-oxo-15-hydroxy-7a,10a-bishomo-19-methyl-13-trans,18                          -prostadienoic acid                                       478   361            9-oxo-15-hydroxy-3-thia-20-nor-13-trans-prostenoic                             acid                                                      479   362            9-oxo-15-hydroxy-3-thia-20-methyl-13-trans-prostenoic                           acid                                                     480   363            9-oxo-15-hydroxy-3-thia-16-ethyl-13-trans-prostenoic                           acid                                                      481   364            9-oxo-15-hydroxy-3-thia-16-methyl-18,19,20-trinor-13-                          trans-prostenoic acid                                     482   365            9-oxo-15-hydroxy-3-thia-19-methyl-13-trans,18-prostad                          ienoic acid                                               483   366            9-oxo-15-hydroxy-3-thia-19,20-dinor-13-trans,17-prost                          adienoic acid                                             484   367            9-oxo-15-hydroxy-20-nor-5-cis,13-trans-prostadienoic                           acid                                                      485   368            9-oxo-15-hydroxy-20-methyl-5-cis,13-trans-prostadieno                          ic acid                                                   486   369            9-oxo-15-hydroxy-16-ethyl-5-cis,13-trans-prostadienoi                          c acid                                                    487   370            9-oxo-15-hydroxy-16-methyl-20-nor-5-cis,13-trans-pros                          tadienoic acid                                            488   371            9-oxo-15-hydroxy-19-methyl-5-cis,13-trans,18-prostatr                          ienoic acid                                               489   372            9-oxo-15-hydroxy-18,19-dimethyl-5-cis,13-trans-18-pro                          statrienoic acid                                          490   373            9-oxo-15-hydroxy-19,20-dinor-5-cis,13-trans,17-prosta                          trienoic acid                                             491   374            9-oxo-15-hydroxy-5-cis,-13-trans,17-cis-prostatrienoi                          c acid                                                    ______________________________________                                    

EXAMPLE 492 Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org. Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbled isobutylene at a fast rate until the solution is saturated. The solution is cooled and 2 ml. of concentrated sulfuric acid is added. The solution is stoppered and allowed to stand at room temperature for 3 days. After the solution is poured into 300 ml. of 5% sodium carbonate, the organic phase is separated, washed with brine, dried with anhydrous magnesium sulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) of product, b.p. 59°C. (0.008 mm).

EXAMPLE 493 Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g. of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether under nitrogen atmosphere, is added 4.0 g. of copper iodide-tri-n-butylphosphine complex followed by dropwise addition of 49 g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv. Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18 hours. Saturated ammonium chloride (110 ml.) is added followed by 100 ml. of water and 100 ml. of diethyl ether. Unreacted magnesium is removed by filtration. The ethereal layer is washed successively with aqueous sodium thiosulfate solution, ammonium chloride solution, and water, dried over magnesium sulfate and taken to dryness to give an oil. Distillation at 0.05 mm. (bath 100°-185°C.) gives 45.4 g. of material containing unreacted starting material and 30 g. (85% yield based on non-recovered starting material; see below) of residue which contains the desired product. This material is chromatographed on silica gel. The product is eluted with diethyl ether to give 25.2 g. (71% based on recovered starting material) of a syrup; this material has no significant ultraviolet absorption; λ_(max) ^(KBr) 5.74, 7.20, 7.35, 8.35 μ; nmr 2H quartet δ4.09 (OCH₂ of ester), 1H broad singlet 3.57 (carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next to C=O), 3H triplet 1.22 (CH₃ of ethyl), 9H singlet 1.17 (CH₃ 's to t-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

EXAMPLE 494 Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethyl ester in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1 hour and is then poured into 500 ml. of ice water and extracted several times with chloroform. The combined chloroform extracts are washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and taken to dryness. The resulting oil is dissolved in 200 ml. of 1N ammonium hydroxide in ethanol, kept at ambient temperature for 15 minutes, then taken to dryness. The residual oil is dissolved in chloroform and washed with 1N hydrochloric acid, saturated sodium chloride solution, dried and taken to dryness to give 21.7 g. (100%) of product as a yellow syrup. There is essentially no uv absorption; λ_(max) ^(KBr) 2.90, 5.75, 8.45 μ ; nmr 2H quartet δ4.13 (OCH₂ of ester), 1H broad singlet 3.63 (carbinolic proton), 3H triplet (CH₃ of ester), and 3 H distorted triplet 0.92 (terminal methyl); mass spectrum: m/e 368.

EXAMPLE 495 Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester in 230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassium hydroxide is stirred at 50°C. for 1 hour and then at room temperature for 18 hours. The resulting solution is acidified with 1N hydrochloric acid, saturated with sodium chloride, and extracted several times with diethyl ether. The combined ether extracts are washed twice with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and taken to dryness to give 13.1 g. (94%) of product as an oil. There is essentially no uv absorption; [α]_(D) ²⁵ 0°(1.0% in CHCl₃); λ_(max) ^(KBr) 2.80-3.70 (Broad), 5.75, 5.87 μ; nmr 2H singlet δ6.65 (hydroxyl and carboxyl protons), 1H broad singlet 3.63 (carbinolic proton), and 3H distorted triplet 0.93 (terminal methyl); mass spectrum: m/e 340.

EXAMPLE 496 Preparation of 1-chloro-3-hydroxy-4-octyne

To 68 ml. of 1.6M butyllithium in hexane at -50°C. is added dropwise, with stirring, 7.4 g. of 1-pentyne. The resulting white sludge is diluted with 20 ml. of hexane, brought to 10°C. and treated with 11 g. of freshly prepared β-chloropropionaldehyde (Org. Syn., Coll. Vol. I, p. 166) at such a rate that the temperature is maintained at 10°-Coll. C. The solution is allowed to stir at ambient temperature for 18 hours then treated with saturated ammonium chloride solution. The organic phase is separated, washed with dilute hydrochloric solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation gives 5.1 g. of product b.p. 65°-66°C. at 0.3 nm.; λmax. 2.95 (-OH) and 4.55 μ (--C.tbd.C--); vapor phase chromatography shows one peak.

EXAMPLE 497 Preparation of 1-chloro-3-hydroxy-4-cis-octene

A solution of 2 g. of 1-chloro-3-hydroxy-4-octyne (Example 496) is hydrogenated in 50 ml. absolute alcohol using 200 mg. of Lindlar catalyst (5% Pd on CaCO₃). The catalyst is removed by filtration and the mother liquor is taken to dryness to give 2 g. of an oil; λmax. 2.95 (--OH) and 7.25 μ ##EQU21##

EXAMPLE 498 Preparation of 3-hydroxy-1-iodo-4-octyne

A mixture of 15 g. of sodium iodide in 100 ml. of 2-butanone is stirred at the reflux temperature for 30 minutes. To the cooled mixture is added 12 g. of 1-chloro-3-hydroxy-4-octyne in 150 ml. of 2-butanone. The resulting mixture is stirred at the reflux temperature for 18 hours then cooled and filtered. The mother liquor is taken to dryness and the residue is triturated with benzene and filtered. The benzene is taken to dryness to give the subject product as an oil. The material is shown to be homogeneous by vapor phase chromatography and thin layer chromatography.

EXAMPLE 499 Preparation of 3-hydroxy-1-iodo-4-cis-octen

The subject compound is prepared from 3-hydroxy-1-chloro-4-cis-octene and sodium iodide by the method of Example 498.

EXAMPLE 500 Preparation of 3-t-butoxy-1-iodo-4-octyne

The subject compound is prepared from 3-hydroxy-1-iodo-4-octyne (Example 498) and isobutylene by the method of Example 492.

EXAMPLE 501 Preparation of 3-t-butoxy-1-iodo-4-cis-octene

The subject compound is prepared from 3-hydroxy-1-iodo-4-cis-octent (Example 499) and isobutylene by the method of Example 492.

EXAMPLE 502

Preparation of 3(tert-butoxy)-1-iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et. al., Bull. Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing 30 g. of sodium iodide is stirred at the reflux temperature for 18 hours. The cooled solution is filtered and the mother liquor is taken to dryness. Distillation of the residue affords 32.9 g. (84%) of 1-iodo-3-hexanol, b.p. 105°C. (10 mm). Treatment of this material in 500 ml. of methylene chloride, containing 4 ml. of concentrated sulfuric acid, with isobutylene according to the procedure described in Example 492 gives 27 g. of crude material. Chromatography on florisil affords 16 g. of product; λmax. 7.22 and 7.37 μ(tert-butyl group).

EXAMPLES 503- 558

Treatment of the cyclopentenones designated in the table below with the designated Grignard reagents by the procedure of Example 493 is productive of the alkyl 9-oxo-15-t-butoxy-8ξ-prostanoates and prostenoates of the table. 3-t-Butoxyoctylmagnesium iodide was prepared from 3-t-butoxy-1-iodooctane (Example 492); 3-t-butoxyhexyl magnesium iodide was prepared from 3-t-butoxy-1-iodohexane (Example 502), 3-t-butoxy-4-octynyl magnesium iodide was prepared from 3-t-butoxy-1-iodo-4-octyne (Example 500); and 3-t-butoxy-4-cis-octenyl magnesium iodide was prepared from 3-t-butoxy-1-iodo-4-cis-octene (Example 501).

                                      Table 6                                      __________________________________________________________________________          Starting cyclopentenone Product Alkyl 9-Oxo-15-t-butoxy-8ξ-prostan                                  oates,                                            Example                                                                             of Example   Grignard Reagent                                                                          prostynoates and prostenoates                     __________________________________________________________________________     503  31           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-prostan                                  oate                                              504  41           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-pr                                  ostanoate                                         505  46           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-prostanoa                                  te                                                506  70           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-prosta                                  noate                                             507  79           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-prosta                                  noate                                             508  99           3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-prosta                                  noate                                             509  118          3-t-butoxyoctyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-prostano                                  ate                                               510  900          3-t-butoxyoctyl magnesium iodide                                                          methyl 9-oxo-15-t-butoxy-8ξ-5-cis-prosteno                                  ate                                               511  31           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-ethyl-19,20-dinor-8                                  ξ-prostanoate                                  512  41           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-19,20-di                                  nor-8ξ-prostanoate                             513  46           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3-oxa-19,20-dinor-8.x                                  i.-prostanoate                                    514  70           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-fluoro-19,20-dinor-                                  8ξ-prostanoate                                 515  79           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-phenyl-19,20-dinor-                                  8ξ-prostanoate                                 516  99           3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-2-methyl-19,20-dinor-                                  8ξ-prostanoate                                 517  118          3-t-butoxyhexyl magnesium iodide                                                          ethyl 9-oxo-15-t-butoxy-3-thia-19,20-dinor-8.                                  xi.-prostanoate                                   518  900          3-t-butoxyhexyl magnesium iodide                                                          methyl 9-oxo-15-t-butoxy-19,20-dinor-8ξ-5-                                  cis-prostenoate                                   519  13           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate      520  15           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-pr                                  ostynoate                                         521  23           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-1                                  6-prostynoate                                     522  31           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-pros                                  tynoate                                           523  41           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16                                  -prostynoate                                      524  46           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-prosty                                  noate                                             525  53           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-prosty                                  noate                                             526  70           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-pro                                  stynoate                                          527  74           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-pros                                  tynoate                                           528  79           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-pro                                  stynoate                                          529  81           3-t-butoxy-4-octynyl magnesium iodide                                                     butyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate      530  82           3-t-butoxy-4-octynyl magnesium iodide                                                     isopropyl 9-oxo-15-t-butoxy-8ξ-16-prostyno                                  ate                                               531  83           3-t-butoxy-4-octynyl magnesium iodide                                                     methyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                                  4                                                 532  84           3-t-butoxy-4-octynyl magnesium iodide                                                     decyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate      533  99           3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-pro                                  stynoate                                          534  118          3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-prost                                  ynoate                                            535  111          3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-pro                                  stynoate                                          536  113          3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-                                  16-prostynoate                                    537  114          3-t-butoxy-4-octynyl magnesium iodide                                                     ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-                                  16-prostynoate                                    538  900          3-t-butoxy-4-octynyl magnesium iodide                                                     methyl 9-oxo-15-t-butoxy-8ξ-16-yne-5-cis-p                                  rostenoate                                        539  13           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-8ξ                                                  -16-cis-prostenoate                               540  15           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-ci                                  s-prostenoate                                     541  23           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-1                                  6-cis-prostenoate                                 542  31           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-cis-                                  prostenoate                                       543  41           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16                                  -cis-prostenoate                                  544  46           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-cis-pr                                  ostenoate                                         545  53           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-cis-pr                                  ostenoate                                         546  70           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-cis                                  -prostenoate                                      547  74           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-cis-                                  prostenoate                                       548  79           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-cis                                  -prostenoate                                      549  81           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 butyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosteno                                  ate                                               550  82           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 iospropyl 9-oxo-15-t-butoxy-8ξ-16-cis-pros                                  tenoate                                           551  83           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 methyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosten                                  oate                                              552  84           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 decyl 9-oxo-15-t-butoxy-8ξ-16-cis-prosteno                                  ate                                               553  99           3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-cis                                  -prostenoate                                      554  118          3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-cis-p                                  rostenoate                                        555  111          3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-cis                                  -prostenoate -556          113 3-t-butoxy-4-c                                                             is-octenyl                                                                     magnesium                                                                      iodide ethyl                                                                   9-oxo-15-t-butoxy-                                                             10a-homo-7-nor-8.x                                                             i.-16-cis-prosteno                                                             ate                    557  114          3-t-butoxy-4-cis-octenyl magnesium iodide                                                 ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ                                    -16-cis-prostenoate                              558  900          3-t-butoxy-4-cis-octenyl magnesium iodide                                                 methyl 9-oxo-15-t-butoxy-8ξ-5-cis-16-cis-p                                  rostadienoate                                     __________________________________________________________________________

EXAMPLES 559-614

Treatment of the 9-oxo-15-t-butoxy derivatives designated in the table below with trifluoroacetic acid and then with aqueous ammonia by the method described in Example 494 is productive of the 9-oxo-15-hydroxy esters of the table.

                  TABLE 7                                                          ______________________________________                                                Starting 15-t-                                                          Ex-    butoxy derivative                                                                            Product Alkyl 9-oxo-15-                                   ample  of Example                                                              hydroxy derivative                                                             ______________________________________                                         559    503           Ethyl 9-oxo-15-hydroxy-2-ethyl-prostanoate                560    504           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-prostanoate           561    505           Ethyl 9-oxo-15-hydroxy-3-oxa-prostanoate                  562    506           Ethyl 9-oxo-15-hydroxy-2-fluoro-prostanoate               563    507           Ethyl 9-oxo-15-hydroxy-2-phenyl-prostanoate               564    508           Ethyl 9-oxo-15-hydroxy-2-methyl-prostanoate               565    509           Ethyl 9-oxo-15-hydroxy-3-thia-prostanoate                 566    510           Methyl 9-oxo-15-hydroxy-5-cis-prostenoate                 567    511           Ethyl 9-oxo-15-hydroxy-2-ethyl-19,20-dinor-prostanoat                          e                                                         568    512           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-19,20-dinor-prost                          anoate                                                    569    513           Ethyl 9-oxo-15-hydroxy-3-oxa-19,20-dinor-prostanoate                           p                                                         570    514           Ethyl 9-oxo-15-hydroxy-2-fluoro-19,20-dinor-prostanoa                          te                                                        571    515           Ethyl 9-oxo-15-hydroxy-2-phenyl-19,20-dinor-prostanoa                          te                                                        572    516           Ethyl 9-oxo-15-hydroxy-2-methyl-19,20-dinor-prostanoa                          te                                                        573    517           Ethyl 9-oxo-15-hydroxy-3-thia-19,20-dinor-prostanoate                          q                                                         574    518           Methyl 9-oxo-15-hydroxy-19,20-dinor-5-cis-prostenoate                          .                                                         575    519           Ethyl 9-oxo-15-hydroxy-16-prostynoate                     576    520           Ethyl 9-oxo-15-hydroxy-6,7-dinor-16-prostynoate           577    521           Ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-16-prostynoate       578    522           Ethyl 9-oxo-15-hydroxy-2-ethyl-16-prostynoate             579    523           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-16-prostynoate        580    524           Ethyl 9-oxo-15-hydroxy-3-oxa-16-prostynoate               581    525           Ethyl 9-oxo-15-hydroxy-7-nor-16-prostynoate               582    526           Ethyl 9-oxo-15-hydroxy-2-fluoro-16-prostynoate            583    527           Ethyl 9-oxo-15-hydroxy-7a-homo-16-prostynoate             584    528           Ethyl 9-oxo-15-hydroxy-2-phenyl-16-prostynoate            585    529           Butyl 9-oxo-15-hydroxy-16-prostynoate                     586    530           Isopropyl 9-oxo-15-hydroxy-16-prostynoate                 587    531           Methyl 9-oxo-15-hydroxy-16-prostynoate                    588    532           Decyl 9-oxo-15-hydroxy-16-prostynoate                     589    533           Ethyl 9-oxo-15-hydroxy-2-methyl-16-prostynoate            590    534           Ethyl 9-oxo-15-hydroxy-3-thia-16-prostynoate              591    535           Ethyl 9-oxo-15-hydroxy-10a-homo-16-prostynoate            592    536           Ethyl 9-oxo-15-hydroxy-10a-homo-7-nor-16-prostynoate                           N                                                         593    537           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-16-prostynoate                           O                                                         594    538           Methyl 9-oxo-15-hydroxy-16-yne-5-cis-prostenoate          595    539           Ethyl 9-oxo-15-hydroxy-16-cis-prostenoate                 596    540           Ethyl 9-oxo-15-hydroxy-6,7-dinor-16-cis-prostenoate       597    541           Ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-16-cis-prostenoa                          te                                                        598    542           Ethyl 9-oxo-15-hydroxy-2-ethyl-16-cis-prostenoate         599    543           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-16-cis-prostenoat                          e                                                         600    544           Ethyl 9-oxo-15-hydroxy-3-oxa-16-cis-prostenoate           601    545           Ethyl 9-oxo-15-hydroxy-7-nor-16-cis-prostenoate           602    546           Ethyl 9-oxo-15-hydroxy-2-fluoro-16-cis-prostenoate        603    547           Ethyl 9-oxo-15-hydroxy-7a-homo-16-cis-prostenoate         604    548           Ethyl 9-oxo-15-hydroxy-2-phenyl-16-cis-prostenoate        605    549           Butyl 9-oxo-15-hydroxy-16-cis-prostenoate                 606    550           Isopropyl 9-oxo-15-hydroxy-16-cis-prostenoate             607    551           Methyl 9-oxo-15-hydroxy-16-cis-prostenoate                608    552           Decyl 9-oxo-15-hydroxy-16-cis-prostenoate                 609    553           Ethyl 9-oxo-15-hydroxy-2-methyl-16-cis-prostenoate        610    554           Ethyl 9-oxo-15-hydroxy-3-thia-16-cis-prostenoate          611    555           Ethyl 9-oxo-15-hydroxy-10a-homo-16-cis-prostenoate        612    556           Ethyl 9-oxo-15-hydroxy-10a-homo-7-nor-16-cis-prosteno                          ate                                                       613    557           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-16-cis-prosteno                          ate                                                       614    558           Methyl 9-oxo-15-hydroxy-5-cis-16-cis-prostadienoate       ______________________________________                                    

EXAMPLES 615-662

Saponification of the 9-oxo-15-hydroxy alkyl esters designated in the table below by the procedure described in Example 495 is productive of the carboxylic acids of the table.

                  TABLE 8                                                          ______________________________________                                                Starting alkyl                                                          Ex-    ester of      Product 9-oxo-15-hydroxy-                                 ample  Example                                                                 prostanoic acid                                                                ______________________________________                                         615    559           9-oxo-15-hydroxy-2-ethyl-prostanoic acid                  616    560           9-oxo-15-hydroxy-3,3-dimethyl-prostanoic acid             617    561           9-oxo-15-hydroxy-3-oxa-prostanoic acid                    618    562           9-oxo-15-hydroxy-2-fluoro-prostanoic acid                 619    563           9-oxo-15-hydroxy-2-phenyl-prostanoic acid                 620    564           9-oxo-15-hydroxy-2-methyl-prostanoic acid                 621    565           9-oxo-15-hydroxy-3-thia-prostanoic acid                   622    566           9-oxo-15-hydroxy-5-cis-prostenoic acid                    623    567           9-oxo-15-hydroxy-2-ethyl-19,20-dinor-prostanoic                                acid                                                      624    568           9-oxo-15-3,3-dimethyl-19,20-dinor-prostanoic acid         625    569           9-oxo-15-hydroxy-3-oxa-19,20-dinor-prostanoic acid        626    570           9-oxo-15-hydroxy-2-fluoro-19,20-dinor-prostanoic                               acid                                                      627    571           9-oxo-15-hydroxy-2-phenyl-19,20-dinor-prostanoic                               acid                                                      628    572           9-oxo-15-hydroxy-2-methyl-19,20-dinor-prostanoic                               acid                                                      629    573           9-oxo-15-hydroxy-3-thia-19,20-dinor-prostanoic acid       630    574           9-oxo-15-hydroxy-19,20-dinor-5-cis-prostenoic acid        631    575           9-oxo-15-hydroxy-16-prostynoic acid                       632    576           9-oxo-15-hydroxy-6,7-dinor-16-prostynoic acid             633    577           9-oxo-15-hydroxy-7a,7b-bishomo-16-prostynoic acid         634    578           9-oxo-15-hydroxy-2-ethyl-16-prostynoic acid               635    579           9-oxo-15-hydroxy-3,3-dimethyl-16-prostynoic acid          636    580           9-oxo-15-hydroxy-3-oxa-16-prostynoic acid                 637    581           9-oxo-15-hydroxy-7-nor-16-prostynoic acid                 638    582           9-oxo-15-hydroxy-2-fluoro-16-prostynoic acid              639    583           9-oxo-15-hydroxy-7a-homo-16-prostynoic acid               640    584           9-oxo-15-hydroxy-2-phenyl-16-prostynoic acid              641    589           9-oxo-15-hydroxy-2-methyl-16-prostynoic acid              642    590           9-oxo-15-hydroxy-3-thia-16-prostynoic acid                643    591           9-oxo-15-hydroxy-10a-homo-16-prostynoic acid              644    592           9-oxo-15-hydroxy-10a-homo-7-nor-16-prostynoic acid        645    593           9-oxo-15-hydroxy-7a,10a-bishomo-16-prostynoic acid        646    594           9-oxo-15-hydroxy-16-yne-5-cis-prostenoic acid             647    595           9-oxo-15-hydroxy-16-cis-prostenoic acid                   648    596           9-oxo-15-hydroxy-6,7-dinor-16-cis-prostenoic acid         649    597           9-oxo-15-hydroxy-7a,7b-bishomo-16-cis-prostenoic                               acid                                                      650    598           9-oxo-15-hydroxy-2-ethyl-16-cis-prostenoic acid           651    599           9-oxo-15-hydroxy-3,3-dimethyl-16-cis-prostenoic                                acid                                                      652    600           9-oxo-15-hydroxy-3-oxa-16-cis-prostenoic acid             653    601           9-oxo-15-hydroxy-7-nor-16-cis-prostenoic acid             654    602           9-oxo-15-hydroxy-2-fluoro-16-cis-prostenoic acid          655    603           9-oxo-15-hydroxy-7a-homo-16-cis-prostenoic acid           656    604           9-oxo-15-hydroxy-2-phenyl-16-cis-prostenoic acid          657    609           9-oxo-15-hydroxy-2-methyl-16-cis-prostenoic acid          658    610           9-oxo-15-hydroxy-3-thia-16-cis-prostenoic acid            659    611           9-oxo-15-hydroxy-10a-homo-16-cis-prostenoic acid          660    612           9-oxo-15-hydroxy-10a-homo-7-nor-16-cis-prostenoic                              acid                                                      661    613           9-oxo-15-hydroxy-7a,10a-bishomo-16-cis-prostenoic                              acid                                                      662    614           9-oxo-15-hydroxy-5-cis-16-cis-prostadienoic               ______________________________________                                                              acid                                                 

EXAMPLE 663 Ethyl 9-oxo-15-hydroxy-16-trans-prostenoate

To a mixture of 1 g. of ethyl 9-oxo-15 hydroxy -16 -prostynoate (Example 575), 11 ml. of water and 27 ml. of dimethylformamide is added 27 ml. of 0.45 N chromous sulfate solution. The mixture is stirred for 48 hours under nitrogen atmostphere. The mixture then is extracted with ether several times and the combined extracts are taken to dryness. Silica gel chromatography gives the subject product as an oil.

EXAMPLES 664 - 682

Treatment of the 9-oxo-15-hydroxy-16-prostynoates listed in Table 8A below with chromous sulfate in the manner of Example 663 is productive of the product 9-oxo-15-hydroxy-16-trans-prostenoates of the table.

                  TABLE 8A                                                         ______________________________________                                                Starting      Product                                                   Ex-    16-prostenoate                                                                               9-oxo-15-hydroxy-16-                                      ample  of Example    trans-prostenoate                                         ______________________________________                                         664    576           Ethyl 9-oxo-15-hydroxy-6,7-dinor-16-trans-prostenoate                          N                                                         665    577           Ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-16-trans-prosten                          oate                                                      666    578           Ethyl 9-oxo-15-hydroxy-2-ethyl-16-trans-prostenoate       667    579           Ethyl 9-oxo-15-hydroxy-3,3-dimethyl-16-trans-prosteno                          ate                                                       668    580           Ethyl 9-oxo-15-hydroxy-3-oxa-16-trans-prostenoate         669    581           Ethyl 9-oxo-15-hydroxy-7-nor-16-trans-prostenoate         670    582           Ethyl 9-oxo-15-hydroxy-2-fluoro-16-trans-prostenoate                           e                                                         671    583           Ethyl 9-oxo-15-hydroxy-7a-homo-16-trans-prostenoate       672    584           Ethyl 9-oxo-15-hydroxy-2-phenyl-16-trans-prostenoate                           n                                                         673    585           Butyl 9-oxo-15-hydroxy-16-trans-prostenoate               674    586           Isopropyl 9-oxo-15-hydroxy-16-trans-prostenoate           675    587           Methyl 9-oxo-15-hydroxy-16-trans-prostenoate              676    588           Decyl 9-oxo-15-hydroxy-16-trans-prostenoate               677    589           Ethyl 9-oxo-15-hydroxy-2-methyl-16-trans-prostenoate                           t                                                         678    590           Ethyl 9-oxo-15-hydroxy-3-thia-16-trans-prostenoate        679    591           Ethyl 9-oxo-15-hydroxy-10a-homo-16-trans-prostenoate                           .                                                         680    592           Ethyl 9-oxo-15-hydroxy-10a-homo-7-nor-16-trans-proste                          noate                                                     681    593           Ethyl 9-oxo-15-hydroxy-7a,10a-bishomo-16-trans-proste                          noate                                                     682    594           Methyl 9-oxo-15-hydroxy-5-cis,16-trans-prostadienoate     ______________________________________                                    

EXAMPLES 683-698

Saponification of the alkyl 9-oxo-15-hydroxy-16-trans-prostenoates listed in Table 8B below by the procedure described in Example 495 is productive of the corresponding prostenoic acids of the table.

                  TABLE 8B                                                         ______________________________________                                                Starting      Product 9-oxo-15-                                         Ex-    alkyl ester   hydroxy-16-trans                                          ample  of Example    prostenoic acids                                          ______________________________________                                         683    663           9-oxo-15-hydroxy-16-trans-prostenoic acid                 684    664           9-oxo-15-hydroxy-6,7-dinor-16-trans-prostenoic acid       685    665           9-oxo-15-hydroxy-7a,7b-bishomo-16-trans-prostenoic                             acid                                                      686    666           9-oxo-15-hydroxy-2-ethyl-16-trans-prostenoic acid         687    667           9-oxo-15-hydroxy-3,3-dimethyl-16-trans-prostenoic                              acid                                                      688    668           9-oxo-15-hydroxy-3-oxa-16-trans-prostenoic acid           689    669           9-oxo-15-hydroxy-7-nor-16-trans-prostenoic acid           690    670           9-oxo-15-hydroxy-2-fluoro-16-trans-prostenoic acid        691    671           9-oxo-15-hydroxy-7a-homo-16-trans-prostenoic acid         692    672           9-oxo-15-hydroxy-2-phenyl-16-trans-prostenoic acid        693    677           9-oxo-15-hydroxy-2-methyl-16-trans-prostenoic acid        694    678           9-oxo-15-hydroxy-3-thia-16-trans-prostenoic acid          695    679           9-oxo-15-hydroxy-10a-homo-16-trans-prostenoic acid        696    680           9-oxo-15-hydroxy-10a-homo-7-nor-16-trans-prostenoic                            acid                                                      697    681           9-oxo-15-hydroxy-7a,10a-bishomo-16-trans-prostenoic                            acid                                                      698    682           9-oxo-15-hydroxy-5-cis,16-trans-prostadienoic             ______________________________________                                                              acid                                                 

EXAMPLE 699 Preparation of 9-oxo-15-hydroxy-3,3-dimethylprostanoic acid

A 2 g. sample of 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acid is hydrogenated using 700 mg. of 10% palladium on carbon in 50 ml. of absolute alcohol. The catalyst is removed by filtration and the mother liquor is taken to dryness to give 2 g. of subject compound as an oil.

EXAMPLE 723 Preparation of 1-chloro-trans-1-octen-3-one

To a slurry of 233.5 g. (1.75 moles) of aluminum chloride in 390 ml. of carbon tetrachloride, saturated with acetylene and cooled in an ice bath, is added over 20 minutes 201.9 g. (1.50 moles) of hexanoyl chloride. After the addition is complete, acetylene is bubbled into the mixture as rapidly as it is absorbed and for 1 hour after absorption becomes slow. The mixture is poured onto 1700 g. of ice and 720 ml. of saturated brine. The organic phase is separated and the aqueous phase is washed with ether. The combined organic phase and washings are washed with saturated brine, dried (Na₂ SO₄) and evaporated. The residual oil is combined with 10 g. of hydroquinone and distilled to yield a colorless oil, b.p. 51°-52°C. (0.10 torr).

EXAMPLE 724 Preparation of 1-iodo-trans-1-octen-3-one

A mixture of 54.5 g. (0.364 mole) of sodium iodide and 40 g. (0.249 mole) of 1-chloro-trans-1-octen 3-one (Example 723) in 360 ml. of acetone is stirred and refluxed for 24 hours. The reaction mixture is cooled, filtered and concentrated. The residue is partitioned between water and ether. The organic phase is washed with dilute sodium bicarbonate solution, brine, dried (MgSO₄) and evaporated to an oil. This material is used directly without purification.

EXAMPLE 725 Preparation of 1-bromo-trans-1-octen-3 one

A mixture of 68.0 g. (0.424 mole) of 1-chloro-trans-1-octen-3 one (Example 723) and 444 g. (4.24 moles) of anhydrous lithium bromide in 900 ml. of 2-pentanone is refluxed for 30 minutes, cooled, and partitioned between ice water and ether. The organic phase is washed with water and saturated brine, dried (NaSO₄), and evaporated to an oil. This material is used directly without purification.

EXAMPLE 726 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 14.29 g. (0.378 mole) of sodium borohydride in 400 ml. of anhydrous ethanol is added the crude 1-bromo-trans-1-octen-3-one (Example 725), from 0.424 mole of 1-chloro-trans-1-octen-3-one) over 30 minutes. The mixture is stirred for 2 hours with ice cooling and is then partitioned between ice water and benzene. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to an oil. Fractional distillation yields the title compound as a colorless oil, b.p. 66°-68°C. (0.025 torr).

EXAMPLE 727 Preparation of 1-chloro-trans-1-octen-3-ol

Treatment of 1-chloro-trans-1-octen-3-one (Example 723) with sodium borohydride in the manner of Example 726 is productive of the subject compound.

EXAMPLE 728 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-octene

A mixture of 6.212 g. (0.030 mole) of 1-bromo-trans-1-octen-3-ol (Example 726) and 10.67 g. (0.033 mole) of triphenylmethyl bromide in 40 ml. of pyridine is heated to 100°C. for 1.5 hours under an inert atmosphere. The mixture is cooled and filtered. The filtrate is partitioned between ice water and ether. The organic phase is washed with cold dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine, dried (NaSO₄ ), and evaporated to an oil. The latter is dissolved in hexane and passed through 250 g. of Florisil to yield after evaporation a colorless oil. Found for C₂₇ H₂₉ OBr : C, 72.13; H, 6.61; BR, 17.57.

EXAMPLE 729 Preparation of 1-iodo-trans-1-octen-3-ol

Treatment of 63 g. (0.25 mole) of 1-iodo-trans-1-octen-3-one (Example 724) with sodium borohydride in the manner described in Example 726 gave 58 g. of yellow oil. The oil is purified by adsorption chromatography on a magnesia silica gel column using benzene as eluent to give a light yellow oil.

EXAMPLE 730 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 7.62 g. (0.03 mole) of 1-iodo-trans1-octen-3-ol with 10.67 g. (0.033 mole) of triphenylmethyl bromide in pyridine in the manner described in Example 728 gave 13.448 g. (90%) of a colorless oil.

EXAMPLE 731 Preparation of 1-chloro-3-triphenylmethoxy-trans-1-octene

Treatment of 1-chloro-trans-1-octen-3-ol (Example 727) with triphenylmethyl chloride by the method described in Example 728 except that the heating period is extended to six hours provides the subject compound.

EXAMPLE 732 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.535 g. (0.022 g. atom) of magnesium in 6 ml. of tetrahydrofuran is added under an inert atmosphere 2 ml. of a solution of 6.548 g. (0.01455 mole) of 1-bromo-3-trityloxy-trans-1-octene (Example 728) in 8 ml. of tetrahydrofuran. Reaction is initiated by warming the mixture to 45°C. and adding 1 drop of methyl iodide. The remainder of the halide is added at a rate to maintain a temperature of 43°-46°C. and the mixture is heated at 45°C. for 1 hour after complete addition of the halide. The Grignard reagent is cooled and added to an ice cooled solution of 2.615 g. (0.0117 mole) of 2-(6-carbomethoxyhexyl) 2-cyclopentenone (Example 83) and 0.229 g. of Copper (I) iodide-tri-in-butylphosphine in 6 ml. of ether over 6 minutes. The mixture is stirred with ice cooling for 30 minutes and poured into 200 ml. of saturated ammonium chloride. The mixture is extracted into ether and the organic phase is washed with water and saturated brine, dried (NaSO₄) and evaporated. The residual oil is heated to 80°C. for 30 minutes with 80% aqueous acetic acid under an inert atmosphere. This mixture is cooled, evaporated to dryness, and the residue is separated by dry column chromatography on silica gel using benzene-ethyl acetate 4:1 as eluent. The title compounds are isolated as oils with Δ13 trans/Δ13 cis in ratio of 10:1. Complete resolution is effected with partition chromatography [for a description see M. J. Weiss et al., Tetrahedron, 20, 357 (1964)] on acid-washed Celite -545 using heptane: acetonitrile (Hold Back Volume=1000 ml.); 11-deoxy-prostaglandin-E₁ methyl ester is obtained in Hold Back Volume 3-5 and methyl 15-hydroxy-9-oxo-13-cis-prostenoate is obtained in Hold Back Volume 6-8.

EXAMPLE 733 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.243 g. (0.010 g. atom) of magnesium in 4 ml. of tetrahydrofuran is added under an inert atmosphere 2ml. of a solution of 4.494 g. (0.010 mole) of 1-bromo-3-trityloxy-trans-1-octene in 4 ml. of tetrahydrofuran. Reaction is initiated by warming the mixture to 65°C and adding 1 drop of methyl iodide. The remainder of the halide is added at a rate to maintain a temperature of 65°-70°C. and the mixture is heated at 75°-80°C. for 30 minutes after complete addition of the halide. The Grignard reagent is cooled and added to 2.243 g. (0.010 mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone and 0.200 g. of copper (I) iodide-tri-n-butylphosphine in 6 ml. of ether and worked up with saturated ammonium chloride solution and aqueous acetic acid in the manner of Example 121. The products are isolated as described in Example 732 to yield 11-deoxy-prostaglandin E₁ methyl ester and methyl 15-hydroxy-9-oxo-13-cis-prostenoate in a ratio of 2:1.

EXAMPLE 734 Preparation of 15-hydroxy-9-oxo-13-cis-prostenoic acid

Methyl 15-hydroxy-9-oxo-13-cis-prostenoic acid is treated with potassium hydroxide in aqueous methanol and worked up as described in Example 495 to yield the title compound, m.p. at 71°-75°C.

EXAMPLE 735 Preparation of Prostaglandin-E₁ and 9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

A Grignard reagent is prepared as described in Example 732 from 0.535 g. (0.022 g. atom) of magnesium, 6.742 g. (0.015 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 11 ml. of tetrahydrofuran at a temperature of 40°-42°C. The Grignard reagent is added to 3.95 g. of 2-(6-carbotetrahydropyranyloxyhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone (Example 95) and 0.589 g. of copper (I) iodide tri-n-butylphosphine in 10 ml. of tetrahydrofuran and is worked up with ammonium chloride as described in Example 732. The protecting groups are removed by treating the worked up material, as described in Example 121, with 320 mol of acetic acid-water-tetrahydrofuran 2:1:1 at 45°C. and the products are isolated by chromatography on silica gel with a benzene-ethyl acetate gradient and resolved via partition chromatography on acid-washed Celite 545.

EXAMPLE 736 Preparation of Prostaglandin-E₁, and 9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

Treatment of 2-(6-carbotetrahydropyranylhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone (Example 95) with the Grignard reagent prepared from 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in the presence of Copper (I) iodide tri-n-butylphosphine complex by the procedure described in Example 733 is productive of the subject compounds.

EXAMPLE 737 Preparation of 9α,15-dihydroxy-13-trans-prostenoic acid

To a solution of 433 mg. of 9-oxo-15-hydroxy-13-trans-prostenoic acid in 4.5 ml. of tetrahydrofuran, stirred in an ice bath under nitrogen atmosphere, is added dropwise 3.7 ml. of 0.76M lithium perhydro-9b-boraphenalylhydride. After 40 minutes at 0°C. there is added 1.62 ml. of 3N sodium hydroxide followed by 1.62 ml. of 30% hydrogen peroxide. Ether is added and the resulting solution is acidified with 2N hydrochloric acid. The ether layer is washed several times with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness to give the subject product as an oil.

EXAMPLES 738-893

Treatment of the 9-oxo derivatives designated in the table below with lithium perhydro-9b-boraphenalyl hydride by the procedure described in Example 737 provides the 9α,15 -dihydroxy derivatives of the table.

                  TABLE 9                                                          ______________________________________                                                Starting 9-oxo-                                                         Ex-    derivative of Product 9α, 15-Dihydroxy                            ample  Example       Derivative                                                ______________________________________                                         738    375           9α,15-dihydroxy-5,6,7-trinor-13-trans-prostenoi                          c acid                                                    739    376           9α,15-dihydroxy-7a,7b-bishomo-3-trans-prostenoi                          c acid                                                    740    377           9α,15-dihydroxy-2-ethyl-13-trans-prostenoic                              acid                                                      741    378           9α,15-dihydroxy-3,3-dimethyl-13-trans-prostenoi                          c acid                                                    742    379           9α,15-dihydroxy-3-oxa-13-trans-prostenoic                                acid                                                      743    380           9α,15-dihydroxy-7-nor-13-trans-prostenoic                                acid                                                      744    381           9α,15-dihydroxy-2-fluoro-13-trans-prostenoic                             acid                                                      745    382           9α,15-dihydroxy-7a-homo-13-trans-prostenoic                              acid                                                      746    383           9α,15-dihydroxy-2-phenyl-13-trans-prostenoic                             acid                                                      747    384           9α,15-dihydroxy-2-methyl-13-trans-prostenoic                             acid                                                      748    385           9α,15-dihydroxy-10a-homo-13-trans-prostenoic                             acid                                                      749    386           9α,15-dihydroxy-10a-homo-5,6,7-trinor-13-trans-                          prostenoic acid                                           750    387           9α,15-dihydroxy-10a-homo-7-nor-13-trans-prosten                          oic acid                                                  751    388           9α,15-dihydroxy-7a,10a-bishomo-13-trans-prosten                          oic acid                                                  752    389           9α,15-dihydroxy-3-thia-13-trans-prostenoic                               acid                                                      753    390           9α,15-dihydroxy-13-trans-prostenoic acid            754    391           9α,15-dihydroxy-13-trans-prostenoic acid            755    392           9α,15-dihydroxy-13-trans-prostenoic acid            756    393           9α,15-dihydroxy-13-trans-prostenoic acid            757    394           9α,15-dihydroxy-5-cis,13-trans-prostadienoic                             acid                                                      758    395           9α,15-dihydroxy-20-nor-13-trans-prostenoic                               acid                                                      759    396           9α,15-dihydroxy-20-methyl-13-trans-prostenoic                            acid                                                      760    397           9α,15-dihydroxy-16-ethyl-13-trans-prostenoic                             acid                                                      761    398           9α,15-dihydroxy-16-methyl-20-nor-13-trans-prost                          enoic acid                                                762    399           9α,15-dihydroxy-19-methyl-13-trans,                                      18-prostadienoic acid                                     763    400           9α,15-dihydroxy-18,19-dimethyl-13-trans,                                 18-prostadienoic acid                                     764    401           9α,15-dihydroxy-13-trans,17-cis-prostadienoic                            acid                                                      765    402           9α,15-dihydroxy-5,6,7-trinor-13-trans,                                   17-cis-prostadienoic acid                                 766    403           9α,15-dihydroxy-6,7-dinor-13-trans,                                      17-cis-prostadienoic acid                                 767    404           9α,15-dihydroxy-7a,7b-bishomo-13-trans,                                  17-cis-prostadienoic acid                                 768    405           9α,15--dihydroxy-2-ethyl-13-trans,                                       17-cis-prostadienoic acid                                 769    406           9α,15-dihydroxy-3,3-dimethyl-13-trans,                                   17-cis-prostadienoic acid                                 770    407           9α,15-dihydroxy-3-oxa-13-trans,                                          17-cis-prostadienoic acid                                 771    408           9α,15-dihydroxy-7-nor-13-trans,                                          17-cis-prostadienoic acid                                 772    409           9α,15-dihydroxy-2-fluoro-13-trans,                                       17-cis-prostadienoic acid                                 773    410           9α,15-dihydroxy-7a-homo-13-trans,                                        17-cis-prostadienoic acid                                 774    411           9α,15-dihydroxy-2-phenyl-13-trans,                                       17-cis-prostadienoic acid                                 775    412           9α,15-dihydroxy-2-methyl-13-trans,                                       17-cis-prostadienoic acid                                 776    413           9α,15-dihydroxy-10a-homo-13-trans,                                       17-cis-prostadienoic acid                                 777    414           9α,15-hydroxy-102-homo-5,6,7-trinor-13-trans,                            17-cis-prostadienoic acid                                 778    415           9α,15-dihydroxy-10a-homo-7-nor-13-trans,                                 17-cis-prostadienoic acid                                 779    416           9α,15-dihydroxy-7a,10a-bishomo-13-trans,                                 17-cis-prostadienoic acid                                 780    417           9α,15-dihydroxy-3-thia-13-trans,                                         17-cis-prostadienoic acid                                 781    418           9α,15-dihydroxy-13-trans,17-cis-prostadienoic                            acid                                                      782    419           9α,15-dihydroxy-13-trans, 17-cis-prostadienoic                           acid                                                      783    420           9α,15-dihydroxy-13-trans, 17-cis-prostadienoic                           acid                                                      784    421           9α,15-dihydroxy-13-trans,17-cis-prostadienoic                            acid                                                      785    422           9α,15-dihydroxy-5,6,7-trinor-19-isobutyl-13-tra                          ns, 18-prostadienoic acid                                 786    423           9α,15-dihydroxy-5,6,7,19,20-pentanor-13-trans,1                          7-prostadienoic acid                                      787    424           9α,15-dihydroxy-19,20-dinor-13-trans,                                    18-prostadienoic acid                                     788    425           9α,15-dihydroxy-17,20-dimethyl-20-isopropenyl-1                          3-trans-prostenoic acid                                   789    426           9α,15-dihydroxy-16-ethyl-6,7,19,20-tetranor-13-                          trans-prostenoic acid                                     790    427           9α,15-dihydroxy-18,19-dimethyl-6,7-dinor-13-tra                          ns, 18-prostadienoic acid                                 791    428           9α,15-dihydroxy-16-ethyl-7a,7b-bishomo-13-trans                          -prostenoic acid                                          792    429           9α,15-dihydroxy-19-methyl-7a,7b-bishomo-13-tran                          s, 18-prostadienoic acid                                  793    430           9α,15-dihydroxy-2-ethyl-19,20-dinor-13-trans-pr                          ostenoic acid                                             794    431           9α,15-dihydroxy-2,20-diethyl-13--trans-prosteno                          ic acid                                                   795    432           9α,15-dihydroxy-2-ethyl-16-methyl-20-nor-13-tra                          ns-prostenoic acid                                        796    433           9α,15-dihydroxy-2-ethyl-18,19-dimethyl-13-trans                          , 18-prostadienoic acid                                   797    434           9α,15-dihydroxy-3,3-dimethyl-18,19,20-trinor-13                          -trans-prostenoic acid                                    798    435           9α,15-dihydroxy-3,3,20-trimethyl-13-trans-prost                          enoic acid                                                799    436           9α,15-dihydroxy-3,3,16-trimethyl-20-nor-13-tran                          s-prostenoic acid                                         800    437           9α,15-dihydroxy-3,3-dimethyl-19-isobutyl-13-tra                          ns, 18-prostadienoic acid                                 801    438           9α,15-dihydroxy-3,3-dimethyl-19,20-dinor-13-tra                          ns, 17-prostadienoic acid                                 802    439           9α,15-dihydroxy-3-oxa-20-nor-13-trans-prostenoi                          c acid                                                    803    440           9α,15-dihydroxy-3-oxa-20-methyl-13-trans-proste                          noic acid                                                 804    441           9α,15-dihydroxy-3-oxa-16-ethyl-13-trans-prosten                          oic acid                                                  805    442           9α,15-dihydroxy-3-oxa-16-methyl-20-nor-13-trans                          -prostenoic acid                                          806    443           9α,15-dihydroxy-3-oxa-19,20-dinor-13-trans,                              17-prostadienoic acid                                     807    444           9α,15-dihydroxy-7,19,20-trinor-13-trans,                                 17-prostadienoic acid                                     808    445           9α,15-dihydroxy-7-nor-18,19-dimethyl-13-trans,                           18,prostadienoic acid                                     809    446           9α,15-dihydroxy-7,18,19,20-tetranor-16-methyl-1                          3-trans-prostenoic acid                                   810    447           9α,15-dihydroxy-2-fluoro-20-nor-13-trans-proste                          noic acid                                                 811    448           9α,15-dihydroxy-2-fluoro-20-ethyl-13-trans-pros                          tenoic acid                                               812    449           9α,15-dihydroxy-2-fluoro-16-ethyl-19,20-dinor-1                          3-trans-prostenoic acid                                   813    450           9α,15-dihydroxy-2-fluoro-16-methyl-20-nor-13-tr                          ans-prostenoic acid                                       814    451           9α,15-dihydroxy-2-fluoro-19-methyl-13-trans,                             18-prostadienoic acid                                     815    452           9α,15-dihydroxy-7a-homo-18,19-dimethyl-13-trans                          , 18-prostadienoic acid                                   816    453           9α,15-dihydroxy-7a-homo-19,20-dinor-13-trans,                            17-prostadienoic acid                                     817    454           9α,15-dihydroxy-2-phenyl-20-nor-13-trans-proste                          noic acid                                                 818    455           9α,15-dihydroxy-2-phenyl-20-ethyl-13-trans-pros                          tenoic acid                                               819    456           9α,15-dihydroxy-2-phenyl-16-ethyl-13-trans-pros                          tenoic acid                                               820    484           9α,15-dihydroxy-20-nor-5-cis,                                            13-trans-prostadienoic acid                               821    485           9α,15-dihydroxy-20-methyl-5-cis,                                         13-trans-prostadienoic acid                               822    486           9α,15-dihydroxy-16-ethyl-5-cis,                                          13-trans-prostadienoic acid                               823    487           9α,15-dihydroxy-16-methyl-20-nor-5-cis,                                  13-trans-prostadienoic acid                               824    488           9α,15-dihydroxy-19-methyl-5-cis, 13-trans,                               18-prostatrienoic acid                                    825    489           9α,15-dihydroxy-18,19-dimethyl-5-cis,                                    13-trans, 18-prostatrienoic acid                          826    490           9α,15-dihydroxy-19,20-dinor-5-cis, 13-trans,                             17-prostatrienoic acid                                    827    491           9α,15-dihydroxy-5-cis, 13-trans,                                         17-cis-prostatrienoic acid                                828    734           9α,15-dihydroxy-13-cis-prostenoic acid              829    735           9α,11α,15-trihydroxy-13-cis-prostenoic                             acid                                                      830    615           9α,15-dihydroxy-2-ethyl-prostanoic acid             831    616           9α,15-dihydroxy-3,3-dimethyl-prostanoic acid        832    617           9α,15-dihydroxy-3-oxa-prostanoic acid               833    618           9α,15-dihydroxy-2-fluoro-prostanoic acid            834    619           9α,15-dihydroxy-2-phenyl-prostanoic acid            835    620           9α,15-dihydroxy-2-methyl-prostanoic acid            836    621           9α,15-dihydroxy-3-thia-prostanoic acid              837    622           9α,15-dihydroxy-5-cis-prostenoic acid               838    623           9α,15-dihydroxy-2-ethyl-19,20-dinor-prostanoic                           acid                                                      839    624           9α,15-dihydroxy-3,3-dimethyl-19,20-dinor-prosta                          noic acid                                                 840    625           9α,15-dihydroxy-3-oxa-19,20-dinor-prostanoic                             acid                                                      841    626           9α,15-dihydroxy-2-fluoro-19,20-dinor-prostanoic                           acid                                                     842    627           9α,15-dihydroxy-2-phenyl-19,20-dinor-prostanoic                           acid                                                     843    628           9α,15-dihydroxy-2-methyl-19,20-dinor-prostanoic                           acid                                                     844    629           9α,15-dihydroxy-3-thia-19,20-dinor-prostanoic                            acid                                                      845    630           9α,15-dihydroxy-19,20-dinor-5-cis-prostenoic                             acid                                                      846    631           9α,15-dihydroxy-16-prostynoic acid                  847    632           9α,15-dihydroxy-6,7-dinor-16-prostynoic acid        848    633           9α,15-dihydroxy-7a,7b-bishomo-16-prostynoic                              acid                                                      849    634           9α,15-dihydroxy-2-ethyl-16-prostynoic acid          850    635           9α,15-dihydroxy-3,3-dimethyl-16-prostynoic                               acid                                                      851    636           9α,15-dihydroxy-3-oxa-16-prostynoic acid            852    637           9α,15-dihydroxy-7-nor-16-prostynoic acid            853    638           9α,15-dihydroxy-2-fluoro-16-prostynoic acid         854    639           9α,15-dihydroxy-7a-homo-16-prostynoic acid          855    640           9α,15-dihydroxy-2-phenyl-16-prostynoic acid         856    641           9α,15-dihydroxy-2-methyl-16-prostynoic acid         857    642           9α,15-dihydroxy-3-thia-16-prostynoic acid           858    643           9α,15-dihydroxy-10a-homo-16-prostynoic acid         859    644           9α,15-dihydroxy-10a-homo-7-nor-16-prostynoic                             acid                                                      860    645           9α,15-dihydroxy-7a,10a-bishomo-16-prostynoic                             acid                                                      861    646           9α,15-dihydroxy-16-yne-5-cis-prostenoic acid        862    683           9α,15-dihydroxy-16-trans-prostenoic acid            863    684           9α,15-dihydroxy-6,7-dinor-16-trans-prostenoic                            acid                                                      864    685           9α,15-dihydroxy-7a,7b-bishomo-16-trans-prosteno                          ic acid                                                   865    686           9α,15-dihydroxy-2-ethyl-16-trans-prostenoic                              acid                                                      866    687           9α,15-dihydroxy-3,3-dimethyl-16-trans-prostenoi                          c acid                                                    867    688           9α,15-dihydroxy-3-oxa-16-trans-prostenoic                                acid                                                      868    689           9α,15-dihydroxy-7-nor-16-trans-prostenoic                                acid                                                      869    690           9α,15-dihydroxy-2-fluoro-16-trans-prostenoic                             acid                                                      870    691           9α,15-dihydroxy-7a-homo-16-trans-prostenoic                              acid                                                      871    692           9α,15-dihydroxy-2-phenyl-16-trans-prostenoic                             acid                                                      872    693           9α,15-dihydroxy-2-methyl-16-trans-prostenoic                             acid                                                      873    694           9α,15-dihydroxy-3-thia-16-trans-prostenoic                               acid                                                      874    695           9α,15-dihydroxy-10a-homo-16-trans-prostenoic                             acid                                                      875    696           9α,15-dihydroxy-10a-homo-7-nor-16-trans-prosten                          oic acid                                                  876    697           9α,15-dihydroxy-7a,10a-bishomo-16-trans-prosten                          oic acid                                                  877    698           9α,15-dihydroxy-5-cis, 16-trans-prostadienoic                            acid                                                      878    647           9α,15-dihydroxy-16-cis-prostenoic acid              879    648           9α,15-dihydroxy-,6,7-dinor-16-cis-prostenoic                             acid                                                      880    649           9α,15-dihydroxy-7a,7b-bishomo-16-cis-prostenoic                           acid                                                     881    650           9α,15-dihydroxy-2-ethyl-16-cis-prostenoic                                acid                                                      882    651           9α,15-dihydroxy-3,3-dimethyl-16-cis-prostenoic                           acid                                                      883    652           9α,15-dihydroxy-3-oxa-16-cis-prostenoic acid        884    653           9α,15-dihydroxy-7-nor-16-cis-prostenoic acid        885    654           9α,15-dihydroxy-2-fluoro-16-cis-prostenoic                               acid                                                      886    655           9α,15-dihydroxy-7a-homo-16-cis-prostenoic                                acid                                                      887    656           9α,15-dihydroxy-2-phenyl-16-cis-prostenoic                               acid                                                      888    657           9α,15-dihydroxy-2-methyl-16-cis-prostenoic                               acid                                                      889    658           9α,15-dihydroxy-3-thia-16-cis-prostenoic acid       890    659           9α,15-dihydroxy-10a-homo-16-cis-prostenoic                               acid                                                      891    660           9α,15-dihydroxy-10a-homo-7-nor-16-cis-prostenoi                          c acid                                                    892    661           9α,15-dihydroxy-7a,10a-bishomo-16-cis-prostenoi                          c acid                                                    893    662           9α,15-dihydroxy-5-cis, 16-cis-prostadienoic                              acid                                                      ______________________________________                                    

EXAMPLE 894 Preparation of 2-carbalkoxy (methyl/ethyl)-b 2-(2-methoxyethyl)-cyclopentan-1-one

Treatment of 2-cyclopentanone carboxylate (mixed methyl and ethyl esters) with 2-methoxyethyl bromide by the method of Example 1 furnishes the subject compound as an oil, b.p. 90°C. (0.1 mm).

EXAMPLE 895 Preparation of 2-(2-methoxyethyl)cyclopentan-1-one

Heating 8 g. of 2-carboalkoxy (methyl/ethyl)2-(2-methoxyethyl)-cyclopentan-1-one (Example 894) in 8 ml. of 20% aqueous hydrochloric acid at reflux for 3.5 hours and isolating the product by the method of Example 2 furnishes the subject compound as an oil, b.p. 45°-50°C. (0.02 mm).

EXAMPLE 896 Preparation of 1-acetoxy-2-(2-methoxyethyl)cyclopent-1-ene

The subject compound is prepared from 2-(2-methoxyethyl)cyclopentan-1-one (Example 895) and acetic anhydride by the procedure of Example 10. The product is an oil, b.p. 60°C. (0.2 mm.)

EXAMPLE 897 Preparation of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one

The enol acetate of Example 896 is brominated and dehydrobrominated by the method described in Example 13. The crude product is then dissolved in methylene chloride and is added at -78°C. to a methylene chloride solution containing about seven molar equivalents of boron tribromide. After one hour at -78°C. the solution is allowed to warm to room temperature and is then kept at ambient temperatures for a total of 18 hours. The mixture is poured into water and extracted with ether. The organic phase is washed with saturated saline solution, then water and is dried. Evaporation of solvents leaves subject product, which is purified by distillation. The combined organic phases are washed with ice cold 5% sodium hydroxide solution, ice cold 5% hydrochloric acid, and saturated sodium chloride solution, dried with anhydrous magnesium sulfate and taken to dryness. Distillation gives a pale yellow oil; λ max 5.85 μ (carbonyl group).

EXAMPLE 898 Preparation of 2-formylmethylcycopent-2-en-1-one

Chromium trioxide (0.6 mol) is added to a stirring solution of (1.2 mol) of anhydrous pyridine in 1500 ml. of anhydrous methylene chloride cooled in an ice bath. The deep red suspension is stirred for 15 minutes at 0°C. and 45 minutes at ambient temperature. A solution of 01.5 mol of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one (Example 897) in 50 ml. of methylene chloride is added, all at once, to the suspension. A black terry deposit is formed immediately. After stirring the mixture for 25 minutes at ambient temperature, the methylene chloride is decanted from the tarry precipitate which is then triturated several times with ether.

EXAMPLE 899 Preparation of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one

A mixture of 0.194 g. (0.007952 mole) of sodium hydride (free of mineral oil) and 5.5 ml. of dimethylsulfoxide is heated to 70°C. until gas evolution ceases under a nitrogen atmosphere. The resulting solution is cooled below room temperature and treated with a solution of 1.400 g. (0.00316 mole) of 4-carboxybutyltriphenyl phosphonium bromide [E. J. Corey et al., J. Am. Chem. Soc., 91, 5675 (1969)] in 6 ml. of dimethylsulfoxide. To the resulting red solution is added 0.00263 mole of 2-formylmethylcyclopent-2-en-1-one (Example 898) in 2 ml. of dimethylsulfoxide and the mixture is stirred at room temperature for 2.25 hours. The mixture is poured into ice water, sodium hydroxide solution is added to pH 12, and the neutral materials are extracted with diethyl ether. The basic phase is acidified with dilute hydrochloric acid and is extracted with diethyl ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to a semicrystalline mass. The latter is triturated with hot hexane, the solids are filtered off, and the filtrate is evaporated to yield the subject product as an oil.

EXAMPLE 900 Preparation of 2-(6-carbomethoxy-2-cis-hexenyl)-cyclopent-2-en-1-one

Treatment of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one (Example 899) with diazomethane in the usual manner as productive of the subject ester.

EXAMPLES 901-909

Hydrogenation of 13-trans-prostenoic acids designated in the table below by the procedure of Example 699 is productive of the prostanoic acids of the table.

                  TABLE 10                                                         ______________________________________                                         Ex-    Starting 13-  Product                                                   ample                                                                          trans-pro-                                                                            Prostanoic                                                                     stenoic acid  Acid                                                             of Example                                                              ______________________________________                                         901    397           9-oxo-15-hydroxy-16-ethyl-prostanoic acid                 902    398           9-oxo-15-hydroxy-16-methyl-20-nor-prostanoic acid         903    400           9-oxo-15-hydroxy-18,19-dimethyl-prostanoic acid           904    426           9-oxo-15-hydroxy-16-ethyl-6,7,19,20-tetranor-prostano                          ic acid                                                   905    428           9-oxo-15-hydroxy-16-ethyl-7a,7b-bishomo-prostanoic                             acid                                                      906    429           9-oxo-15-hydroxy-19-methyl-7a,7b-bishomo-prostanoic                            acid                                                      907    433           9-oxo-15-hydroxy-2-ethyl-18,19-dimethyl-prostanoic                             acid                                                      908    436           9-oxo-15-hydroxy-3,3,16-trimethyl-20-nor-prostanoic                            acid                                                      909    476           9-oxo-15-hydroxy-7a,10a-bishomo-16-methyl-20-nor-pros                          tanoic acid                                               ______________________________________                                    

EXAMPLES 910-915

Treatment of the 9-oxo-alkyl esters designated in the table below with sodium borohydride by the procedure described in Example 257 is productive of the corresponding 9-hydroxy derivative of the table. These products are obtained as 9α- and 9β-hydroxy epimeric mixtures.

                  TABLE 11                                                         ______________________________________                                         Ex-    Starting 9-oxo-                                                                              Product                                                   ample  derivative of 9α/9β-hydroxy derivative                              Example                                                                 ______________________________________                                         910    260           ethyl 9α/9β,15-dihydroxy-2-ethyl-13-trans-                          prostenoate                                               911    261           ethyl 9α/9β,15-dihydroxy-3,3-dimethyl-13-t                          rans-prostenoate                                          912    262           ethyl 9α/9β,15-dihydroxy-3-oxa-13-trans-pr                          ostenoate                                                 913    266           ethyl 9α/9β,15-dihydroxy-2-phenyl-13-trans                          -prostenoate                                              914    272           ethyl 9α/9β,15-dihydroxy-3-thia-13-trans-p                          rostenoate                                                915    284           ethyl 9α/9β,15-dihydroxy-13-trans,                                  17-cis-prostadienoate                                     ______________________________________                                    

EXAMPLES 916-921

Saponification of the ethyl esters designated in the table below by the procedure described in Example 122 furnishes the carboxylic acids of the table.

                  TABLE 12                                                         ______________________________________                                                              Product 9α/9β,15-di-                           Ex-    Starting ethyl                                                                               hydroxy-13-trans-pro-                                     ample  ester of Example                                                                             stenoic acid                                              ______________________________________                                         916    910           9α/9β,15-dihydroxy-2-ethyl-13-trans-proste                          noic acid                                                 917    911           9α/9β,15-dihydroxy-3,3-dimethyl-13-trans-p                          rostenoic acid                                            918    912           9α/9β ,15-dihydroxy-3-oxa-13-trans-prosten                          oic acid                                                  919    913           9α/9β,15-dihydroxy-2-phenyl-13-trans-prost                          enoic acid                                                920    914           9α/9β,15-dihydroxy-3-thia-13-trans-prosten                          oic acid                                                  921    915           9α/9β,15-dihydroxy-13-trans,17-cis-prostad                          ienoic acid                                               ______________________________________                                    

EXAMPLES 922-932

Treatment of the cycloalkenones of Table 13, which follows, with the Grignard reagent, prepared from 1-bromo-3-triphenylmethoxy-trans-1-octene and magnesium according to the procedure of Example 733, hydrolizing the intermediate 15-O-triphenylmethyl derivatives with glacial acetic acid-tetrahydrofura-water (4:2:1) according to the procedure of Example 121, and isolating the products in the manner described in Example 732 is productive of the product 9-oxo-15-hydroxy-13-cis-prostenoates and 9-oxo-15-hydroxy-13-trans-prostenoates of the table.

                                      TABLE 13                                     __________________________________________________________________________     Example                                                                             Starting cyclopentenone                                                                     Product 15-hydroxy-13-cis-                                                                       Product 15-hydroxy-13-trans-                    Ester of Example                                                                            prostenoate ester prostenoate ester                          __________________________________________________________________________     922  23           ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-13-cis-prostenoate                        N                 ethyl 9-oxo-15-hydroxy-7a,7b-bishomo-1                                         3-trans-prostenoate                        923  31           ethyl 9-oxo-15-hydroxy-2-ethyl-13-cis-prostenoate                                                ethyl 9-oxo-15-hydroxy-2-ethyl-13-tran                                         s-prostenoate                              924  41           ethyl 9-oxo-15-hydroxy-3,3-dimethyl-13-cis-prostenoate                                           ethyl 9-oxo-15-hydroxy-3,3-dimethyl                                            13-trans-prostenoate                       925  46           ethyl 9-oxo-15-hydroxy-3-oxa-13-cis-prostenoate                                                  ethyl 9-oxo-15-hydroxy-3-oxa-13-trans-                                         prostenoate                                926  53           ethyl 9-oxo-15-hydroxy-7-nor-13-cis-prostenoate                                                  ethyl 9-oxo-5-hydroxy-7-nor-13-trans-p                                         rostenoate                                 927  70           ethyl 9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoate                                               ethyl 9-oxo-15-hydroxy-2-fluoro-13-tra                                         ns-prostenoate                             928  84           n-decyl 9-oxo-15-hydroxy-13-cis-prostenoate                                                      n-decyl 9-oxo-15-hydroxy-13-trans-pros                                         tenoate                                    929  99           ethyl 9-oxo-15-hydroxy-2-methyl-13-cis-prostenoate                                               ethyl 9-oxo-15-hydroxy-2-methyl-13-tra                                         ns-prostenoate                             930  111          ethyl 9-oxo-15-hydroxy-10a-homo-13-cis-prostenoate                                               ethyl 9-oxo-15-hydroxy-10a-homo-13-tra                                         ns-prostenoate                             931  118          ethyl 9-oxo-15-hydroxy-3-thia-13-cis-prostenoate                                                 ethyl 9-oxo-15-hydroxy-3-thia-13-trans                                         -prostenoate                               932  900          methyl 9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoate                                             methyl 9-oxo-15-hydroxy-5-cis,                                                 13-trans-prostadienoate                    __________________________________________________________________________

EXAMPLES 933-942

Saponification of the 13-cis-prostenoate alkyl esters designated in Table 14 below by the method described in Example 122 is productive of the 13-cis-prostenoic acids of the Table.

                                      TABLE 14                                     __________________________________________________________________________     Example                                                                             Starting 13-cis-prostenoate                                                                    Product 13-cis-prostenoic acids                           933  922             9-oxo-15-hydroxy-7a,7b-bishomo-113-                       cis-prostenoic acid                                                            934  923             9-oxo-15-hydroxy-2-ethyl-13-cis-                          prostenoic acid                                                                935  924             9-oxo-15-hydroxy-3,3-dimethyl-13-cis-                     prostenoic acid                                                                936  925             9-oxo-15-hydroxy-3-oxa-13-cis-prostenoic acid             937  926             9-oxo-15-hydroxy-7-nor-13-cis-prostenoic acid             938  927             9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoic acid          939  929             9-oxo-15-hydroxy-2-methyl-3-cis-prostenoic acid           940  930             9-oxo-15-hydroxy-10a-homo-13-cis-prostenoic acid          941  931             9-oxo-15-hydroxy-3-thia-13-cis-prostenoic acid            942  932             9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoic              __________________________________________________________________________                          acid                                                 

EXAMPLES 943-954

Treatment of the 9-oxo-13-cis-prostenoic acids and esters of Table 15 below with lithium perhydro-9b-boraphenalyl hydride by the procedure described in Example 737 furnishes the 9α,15-dihydroxy-13-cis-prostenoic acids and esters of the table.

                                      TABLE 15                                     __________________________________________________________________________     Example                                                                             Starting 9-oxo-13-cis-                                                                      Product 9α,15-hydroxy-13-cis-prostenoic acid and                         esters                                                       prostenoic derivative                                                               of Example                                                                __________________________________________________________________________     943  933          9,15-dihydroxy-7a,7b-bishomo-13-cis-prostenoic acid          944  934          9,15-dihydroxy-2-ethyl-13-cis-prostenoic acid                945  935          9,15-dihydroxy-3,3-dimethyl-13-cis-prostenoic acid           946  936          9,15-dihydroxy-3-oxa-13-cis-prostenoic acid                  947  937          9,15-dihydroxy-7-nor-13-cis-prostenoic acid                  948  938          9,15-dihydroxy-2-fluoro-13-cis-prostenoic acid               949  939          9,15-dihydroxy-2-methyl-13-cis-prostenic acid                950  940          9,15-dihydroxy-10a-homo-13-cis-prostenoic acid               951  941          9,15-dihydroxy-3-thia-13-cis-prostenoic acid                 952  942          9,15-dihydroxy-5-cis,-13-cis-prostadienoic acid              953  932          methyl 9,15-dihydroxy-5-cis, 13-cis-prostadienoate           954  928          n-decyl 9,15-dihydroxy-13-cis-prostenoate                    __________________________________________________________________________

EXAMPLE 955 Preparation of 1-iodo-trans-1-octen-3-ol

A solution of 78.2 g. (0.310 moles) of 1-iodo-trans-1-octen-3-one (Example 724) in 150 ml. of absolute ethanol is added dropwise over 2 hours to a slurry of 6.49 g. (0.172 moles) of sodium borohydride in 50 ml. of absolute ethanol cooled in an ice bath. After the addition is complete, the mixture is stirred for 2 hours with ice cooling and is then poured into 1 l. of water. The mixture is extracted into benzene and the organic phase is washed with saturated brine, dried (Na₂ SO₄) and evaporated. The resulting oil is dissolved into 400 ml. of absolute ethanol and treated with 5 mole percent of p-carboxyphenylhydrazine at 70°C. for 1.5 hours to remove residual ketone. The mixture is cooled and evaporated and the residue is dissolved into 400 ml. of ether and is filtered. The filtrate is washed with dilute sodium bicarbonate solution and saturated brine, dried (Na₂ SO₄), and evaporated to an oil. This oil is chromatographyed upon 2 Kg. of Florisil packed in hexane and the product is obtained upon elution with benzene Distillation of the product yields a colorless oil, b.p. 74°-76°C. (0.005 tor.).

EXAMPLE 956 Preparation of 1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene

A mixture of 14.92 g. (0.0588 mole) of 1-iodo-trans-1-octen-3-ol (Example 955) and 18.2 g. (0.0588 mole) of p-anisyldiphenylmethyl chloride in 165 ml. of dry pryidine is heated at 60°C. for 18 hours under an inert atmosphere. The mixture is cooled and the solvent is evaporated in vacuo. The residue is partitioned between ether and water, and the organic phase is washed with water and saturated brine, dried (MgSO₄), and evaporated. The residue is chromatographed upon 300 g. of Florisil packed in hexane and the product is eluted with hexane and 4:1 hexane-benzene the yield a colorless oil.

EXAMPLE 957 Preparation of methyl esters of d1-11-deoxyprostaglandin-E₁ and d1-11-deoxy-15-epi-prostaglandin E₁

To a solution of 6.030 g. (0.01215 mole) of 1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 8 ml. of toluene cooled to -78°C. under an inert atmosphere is added 5.2 ml. of a 2.34 M solution of n-butyllithium in hexane. The resulting solution is allowed to warm to -40°C. and is maintained at this temperature for 1 hour. To the solution containing 3-triphenylmethoxy-trans-1-octenyllithium is then added 5.0 ml. of a 2.44 M (0.0122 mole) solution of trimethylaluminum in heptane and the mixture is allowed to warm to -10°C. The mixture containing lithium trimethyl(3triphenylmethoxy-trans-1-octenyl) alanate is then cooled to -78°C. and to it is added a solution of 2.725 g. (0.01215 mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) dissolved in 10 ml. of diethyl ether. The mixture is allowed to warm to room temperature and is stirred at ambient temperature for 18 hours. The mixture is then poured onto ice and diluted hydrochloric acid and is extracted into ether. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to yield a colorless oil. This oil is heated with 100 ml. of 80% aqueous acetic acid at 80°C. for 1 hour under an inert atmosphere. The resulting mixture is cooled and evaporated in vacuo to dryness with 100 ml. of xylene to yield an oil. This oil is dry-column-chromatographed upon 400 g. of silica gel using 4:1 benzene-ethyl acetate as eluent to yield a total of 2.59 g. of d1-11-deoxyprostaglandin E₁ and d1-11-deoxy-15-epiprostaglandin E₁ methyl esters.

EXAMPLE 958 Preparation of 4-(trimethylsiloxy)-2-(6-carbotrimethylsiloxyhexyl) cyclopent-2-en-1-one

To a solution of 5 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one (Example 94) in 10 ml. of dry N,N-dimethylformamide is added 5.4 g. of trimethylsilyl chloride in a nitrogen atmosphere. To the resulting solution cooled in a tap water bath is added 5.05 g. of triethylamine in 10 ml. of N,N-dimethylformamide dropwise. The resulting mixture is stirred at 60°C. in an oil-bath for 2 hours, then at ambient temperatures for 18 hours. Triethylamine hydrochloride is removed by filtration and the filtrate is taken to dryness. The residual oil is distilled to give 2.6 g. of product, b.p. 156°-157°C. (0.07 mm.).

EXAMPLE 958A Preparation of 4-(dimethylisopropylsiloxy)-2-(6-carbodimethylisopropylsiloxyhexyl) cyclopent-2-en-1-one

Treatment of 1 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one in 2 ml. of dry N,N-dimethylformamide containing 1.81 g. of dimethylisopropylsilyl chloride [E. J. C rey, R. K. Varma, J. Amer. Chem. Soc., 93, 7320 (1971)] 1.57 g. of triethylamine in 2 ml. of N,N-dimethylformamide in the manner described in Example 958 gives 1.45 g. of product after two evaporations with toluene.

EXAMPLE 959 Preparation of 4-(dimethyl-t-butylsiloxy)-2-(6-carbodimethyl-t-butylsiloxyhexyl) cyclopent-2-en-1-one

To a 0°C. solution of 2.0 gm. (8.55 mole) 4-hydroxy-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 94) and 3.65 gm. (54 mole) of imidazole in 5 ml. of dimethylformamide is added a slurry consisting of 4.07 gm. (27 mole) of dimethyl-t-butyl chlorosilane in 5 ml. of dimethylformamide. The slurry is rinsed in with an additional 1 ml. of dimethylformamide. The ice-bath is removed and the solution is stirred at 37°C. for 4 hours. The solution is then poured into 140 ml. of water and the aqueous solution is extracted twice with 70 ml. of isomeric hexanes. The organic layers are combined, dried with magnesium sulfate and concentrated in vacuo to an oil. Toluene (50 ml.) is added twice and evaporated in vacuo to remove unwanted low boiling impurities.

The residue is maintained under active vacuum overnight to give 3.38 gm. (7.45 mole) of an oil, that shows no hydroxyl or carboxyl absorption in the infrared. ˜υ max: 1720 cm⁻ ¹ (unsaturated ketone and silyl ester), 840, 815, 795, 780 cm⁻ ¹ (silyl ether and silyl ester).

EXAMPLE 960 Preparation of d1-prostaglandin E₁ and d1-epi-prostaglandin E₁

To a solution of 4.790 g. (0.0091 mole) of 3-(p-anisyldiphenylmethoxy)-trans- 1-iodo-1-octene (Example 956) in 5 ml. of toluene cooled to -78°C. under an inert atmosphere is added 3.9 ml. of 2.34 M n-butyllithium in hexane. The resulting solution is warmed to -40°C. and is maintained at this temperature for 1 hour. To the solution containing 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium is then added 3.6 ml. of a 2.44 M solution of trimethylaluminum in heptane and the mixture is allowed to warm to 0°C. The solution containing lithium trimethyl[3-(p-anisyldiphenylmethoxy) -trans-1-octenyl]alanate is then added to a solution of 3.30 g. (0.00726 mole) of 2-(6-carbo-t-butyldimethylsiloxyhexyl) -4-(t-butyldimethylsiloxy)-2-cyclopentenone (Example 959) dissolved in 10 ml. of ether cooled to -45°C. under an inert atmosphere. The resulting solution is allowed to warm to room temperature and is stirred at ambient temperatures for 17 hours. The solution is then poured onto a mixture of 5 ml. of concentrated hydrochloric acid and 150 g. of ice. This mixture is stirred until the ice melts and is extracted into ether. The organic phase is washed with ice cold water and cold saturated brine, dried (Na₂ SO₄), and is evaporated ( <37°C.) in vacuo. The resulting oil is then heated to 38°C. for 23 hours under an inert atmosphere with 100 ml. of 3:1:1 (V:V:V) acetic acid-tetrahydrofuran-water. The mixture is then evaporated with 150 ml. of xylene in vacuo ( <38°C.) to yield an oil. Chromatography of this oil upon 115 g. of Silic AR CC-4 (Mallinckrodt) using a benzene-ethyl acetate gradient as eluent yields d1-prostaglandin E₁, m.p. 108-112 (from ethyl acetate) and d1-15-epi-prostaglandin E₁.

EXAMPLE 961 Preparation of 3-triphenylmethoxy-trans-1-octenyllithium

To a solution of 4.96 g. of 1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 10 ml. of toluene cooled to -78°C. is added under an inert atmosphere 1 molar equivalent of n-butyllithium dissolved in hexane. The reaction mixture is allowed to warm to -40°C. and is then maintained at that temperature for 1hour to yield a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium.

EXAMPLE 962 Preparation of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

To a solution of 5.26 g. of 1-iodo-3-(p-anisyldiphenylmethoxy)-trans- 1-octene (Example 956) in 10 ml. of toluene, cooled to -78°C., is added under an inert atmosphere 1 molar equivalent of n-butyllithium dissolved in hexane. The reaction mixture is allowed to warm to -40°C. and is maintained at that temperature for 1 hour to yield a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium.

EXAMPLE 963 Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40°C. is added under an inert atmosphere 1 molar equivalent of trimethylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 964 Preparation of lithium [3-p-anisyldiphenylmethoxy)-trans-1 octenyl]-trimethylalanate

To a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans- 1-octenyllithium (Example 962) cooled to -40°C. is added under an inert atmosphere 1 molar equivalent of trimethylaluminum dissolved in hexane to yield a hydrocarbon solution of the title compound.

EXAMPLE 965 Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-tri-n-propylanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40°C. is added under an inert atmosphere 1 molar equivalent of tri-n-propylaluminum dissolved in hexane to yield a hydrocarbon solution of the title compound.

EXAMPLE 966 Preparation of lithium [3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-tri-n-hexylalanate

To a hydrocarbon solution of 3-(p-anisyldiphenylmethoxy)-trans- 1-octenyllithium (Example 962) cooled to -40°C. is added under an inert atmosphere 1 molar equivalent to tri-n-hexylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 967 Preparation of lithium [3-triphenylmethoxy-trans-1-octenyl]-tri-n-decylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) cooled to -40°C. is added under an inert atmosphere 1 molar equivalent of tri-n-decylaluminum dissolved in heptane to yield a hydrocarbon solution of the title compound.

EXAMPLE 968 Preparation of lithium di-(3-triphenylmethoxy-trans-1-octenyl)-dimethylalanate

To a hydrocarbon solution of dimethylaluminum chloride cooled to -78°C. is added under an inert atmosphere 2 molar equivalents of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0°C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 969 Preparation of lithium di-[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-diethylalanate

To a hexane solution of diethylaluminum chloride cooled to -78°C. is added under an inert atmosphere 2 molar equivalents of 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0°C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 970 Preparation of lithium tri-(3-triphenylmethoxy-trans-1-octenyl)-ethylalanate

To a hydrocarbon solution of ethylaluminum dichloride cooled to -78°C. is added under an inert atmosphere 3 molar equivalents of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane solvent. The mixture is allowed to warm to 0°C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 971 Preparation of lithium tetra-(3-triphenylmethoxy-trans-1-octenyl)alanate

Tp a well stirred mixture of anhydrous aluminum chloride and hexane cooled to -78°C. is added under an inert atmosphere 4 molar equivalents of 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved in toluene-hexane The mixture is allowed to warm to 0°C. to yield the title compound.

EXAMPLE 972 Preparation of lithium tetra-(3-p-anisyldiphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexane cooled to -78°C. is added under an inert atmosphere 4 molar equivalents of 3-p-anisyldiphenylmethoxy-trans-1-octenyllithium (Example 962) dissolved in toluene-hexane. The mixture is allowed to warm to 0°C. to yield the title compound.

EXAMPLES 973-981

Substitution of lithium trimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate in Example 957 with the lithium alanates of Examples 964, 965, 966, 967, 968, 969, 970, 971 or 972 is productive of the methyl esters of d,1-11-deoxy-prostaglandin E₁ and d,11-deoxy-15-epi-prostaglandin E₁.

EXAMPLES 982-990

Substitution of lithium trimethyl [3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate of Example 960 with the lithium alanates of Examples 965, 966, 967, 968, 969, 970, 971 or 972 is productive of d,1-prostaglandin-E₁ and d,1-15-epi-prostaglandin E₁.

EXAMPLE 991 Preparation of hexanoyl bromide

A mixture of 300 g. of hexanoic acid and 260 g. of phosphorus tribromide is heated at 80°C. for 1.5 hours with stirring and protection from moisture. The mixture is cooled and the upper phase is decanted into a distilling flask. Distillation of this material yields 400 g. of the colorless acid bromide, b.p. 51°-53°C. (10 torr.).

EXAMPLE 992 Preparation of 1-bromo-trans-1-octen-3-one

A mixture of 300 g. of aluminum bromide and 250 ml. of 1,2-dibromoethane, cooled in an ice bath and protected from moisture, is saturated with acetylene. To the mixture is added with ice cooling 150 g. of hexanoyl bromide (Example 991) over a period of 20 minutes and the resulting mixture is treated with acetylene until gas uptake ceases. The reaction mixture is poured onto 500 ml. of saturated brine and 500 g. of ice. The resulting mixture is extracted twice with 500 ml. of ether. The combined organic extracts are washed twice with 500 ml. of saturated brine and dried with anhydrous sodium sulfate. To the organic phase is added 5 g. of hydroquinone and the solvent is evaporated in vacuo to yield the crude 1-bromo-trans-1-octen-3-one.

EXAMPLE 993 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 20 g. of sodium borohydride in 800 ml. of anhydrous ethanol is added 160 g. of crude 1-bromo-trans-1-octen-3-one (Example 992) over a period of 0.5 hour. The mixture is stirred for 2 hours with ice cooling and is then partitioned between ice water and benzene. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to an oil. Distillation gives the product as an oil, b.p. 66°-68°C. (0.025 torr.).

EXAMPLE 994 Preparation of 4,4-dimethyl-1-octyn-3-ol

To a solution of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediamine complex in 100 ml. of dry dimethylsulfoxide is added 25.6 g. (0.200 mole) of 2,2-dimethyl-1-hexanal, prepared according to the procedure of G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85, 2178 (1963), in 25 ml. of dimethylsulfoxide at a rate to maintain a temperature of 25°C. (cooling). The mixture is then maintained at 25°C. for 2 hours and is poured onto ice and excess hydrochloric acid. The mixture is extracted with ether and the organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to an oil. Distillation in vacuo yields the product as a colorless oil.

EXAMPLE 995 Preparation of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne

To a solution of 23.1 g. (0.150 mole) of 4,4-dimethyl-1-octyn-3-ol (Example 994) in 126 g. of freshly distilled dihydropyran is added 1 drop of phosphorus oxychloride and the solution is maintained at ambient temperature in a tightly stoppered flask for 20 hours. Five drops of triethylamine are then added and the mixture is evaporated in vacuo to an oil. The oil is chromatographed on 600 g. of silica gel and the product is eluted with 5% ethyl acetate in benzene yielding a colorless oil.

EXAMPLE 996 Preparation of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol

To 233 ml. of a 0.43M solution of disiamylborane in diglyme cooled to 0°C. under an inert atmosphere is added 23.8 g. (0.100 mole) 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995). The mixture is allowed to come to room temperature and is stirred at ambient temperature for 3 hours. The solution is cooled to 0°C. and 22.5 g. (0.30 mole) of triethylamine oxide is added portionwise such that the temperature is maintained at 0-5°C. The mixture is stirred at 0°C. for 1 hour and is then poured into 150 ml. of 1 N sodium hydroxide followed immediately by a solution of 25.4 g. (0.100 mole) of iodine in 60 ml. of tetrahydrofuran. The mixture is stirred at ambient temperatures for 0.5 hour and poured into 500 ml. of water. The mixture is decolorized by addition of sodium thiosulfate solution and is extracted into ether. The organic phase is washed with water and the solvent is removed in vacuo. The residue is stirred at room temperature for 20 hours with 900 ml. 3:1:1 tetrahydrofuran-acetic acid-water. The solution is evaporated in vacuo and the residue is chromatographed on silica gel in benzene using 10-20% ethylacetate in benzene.

EXAMPLE 997 Preparation of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 11.2 g. (0.0396 mole) of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol (Example 996) with 12.8 g. of triphenylmethyl bromide in 50 ml. of pyridine and purification on Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 998 Preparation of 5,5-dimethyl-1-octyn -3-ol

Treatment of 20.2 g. (0.220 mole) of lithium acetylide-ethylenediame complex in 100 ml. of dimethylsulfoxide with 25.6 g. (0.200 mole) of 3,3-dimethylhexanal [prepared according to the procedure of A. W. Burgstahler, J. Amer. Chem. Soc., 82, 4681 (1960)] and distillation of the product, all as described in Example 994 yields the title compound.

EXAMPLE 999 Preparation of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne

Treatment of 23.1 g. (0.150 mole) of 5,5-dimethyl-1-octyn-3ol (Example 998) with 126 g. of dihydropyran and 1 drop of phosphorus oxychloride as described in Example 995 gives the title compound.

EXAMPLE 1000 Preparation of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol

Treatment of 23.8 g. (0.100 mole) of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) successively with 233 ml. of 0.43 M disiamylborane in diglyme, 22.5 g. of trimethylamine oxide, 150 ml. of 1 N sodium hydroxide, 25.4 g. of iodine, and 900 ml. of 3:1:1 tetrahydrofuran-acetic acid-water as described in Example 996 gives the title compound.

EXAMPLE 1001 Preparation of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 6.0 g. of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol (Example 1000) with 6.9 g. of triphenylmethyl bromide in 30 ml. of pyridine and purification on Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1002 Preparation of 4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene (Example 997) with n-butyllithium in the manner of Example 961 provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1003 Preparation of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene (Example 1001) with n-butyllithium in the manner of Example 961 provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1004 Preparation of lithium (4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to the method of Example 963 from a hydrocarbon solution of 4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1002) and trimethylaluminum.

EXAMPLE 1005 Preparation of lithium (5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

A hydrocarbon solution of the subject alanate is prepared from a hydrocarbon solution of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl lithium (Example 1003) and trimethylaluminum according to the procedure of Example 963.

EXAMPLES 1006-1031

Treatment of the cycloalkenones of Table 16 which follows with the indicated alanates according to the procedure of Example 957 provides the product 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoates of the table. The intermediate corresponding 15-O-triphenylmethyl derivatives are obtained prior to treatment with aqueous acetic acid.

                  TABLE 16                                                         ______________________________________                                         Exam- Starting cyclo-                                                                               Product from reaction with                                ple   alkenone of    lithium (4,4-Dimethyl-3-                                        Example                                                                  triphenylmethoxy-trans-1-                                                      octenyl)trimethylalanate                                                                            (Example 1004)                                            ______________________________________                                         1006  13             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-13-trans-proste                          noate                                                     1007  23             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-7a,7b-bishomo-1                          3-trans-prostenoate                                       1008  31             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-2-ethyl-13-tran                          s-prostenoate                                             1009  41             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-3,3-dimethyl-13                          -trans-prostenoate                                        1010  46             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-3-oxa-13-trans-                          prostenoate                                               1011  53             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-7-nor-13-trans-                          prostenoate                                               1012  70             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-2-fluoro-13-tra                          ns-prostenoate                                            1013  84             n-decyl 9-oxo-15-hydroxy-16,16-dimethyl-13-trans-pros                          tenoate                                                   1014  99             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-2-methyl-13-tra                          ns-prostenoate                                            1015  111            ethyl 9-oxo-15-hydroxy-16,16-dimethyl-10a-homo-13-tra                          ns-prostenoate                                            1016  118            ethyl 9-oxo-15-hydroxy-16,16-dimethyl-3-thia-13-trans                          -prostenoate                                              1017  900            methyl 9-oxo-15-hydroxy-16,16-dimethyl-                                        5-cis,13-transprostadienoate                              1018  79             ethyl 9-oxo-15-hydroxy-16,16-dimethyl-2-phenyl-13-tra                          ns- prostenoate                                           1019  13             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-13-trans-proste                          noate                                                     1020  23             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-7a,7b-bishomo-1                          3-trans-prostenoate                                       1021  31             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-2-ethyl-13-tran                          s-prostenoate                                             1022  41             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-3,3-dimethyl-13                          -trans-prostenoate                                        1023  46             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-3-oxa-13-trans-                          prostenoate                                               1024  53             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-7-nor-13-trans-                          prostenoate                                               1025  70             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-2-fluoro-13-tra                          ns-prostenoate                                            1026  84             n-decyl 9-oxo-15-hydroxy-17,17-dimethyl-13-trans-pros                          tenoate                                                   1027  99             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-2-methyl-13-tra                          ns-prostenoate                                            1028  111            ethyl 9-oxo-15-hydroxy-17,17-dimethyl-10a-homo-13-tra                          ns-prostenoate                                            1029  118            ethyl 9-oxo-15-hydroxy-17,17-dimethyl-3-thia-13-trans                          -prostenoate                                              1030  900            methyl 9-oxo-15-hydroxy-17,17-dimethyl-                                        5-cis,13-trans-prostadienoate                             1031  79             ethyl 9-oxo-15-hydroxy-17,17-dimethyl-2-phenyl-13-tra                          ns-prostenoate                                            ______________________________________                                    

EXAMPLES 1032-1055

Saponification of the 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoate alkyl esters of Table 17 below by the method of Example 122 provides the corresponding prostenoic acids of the Table.

                  TABLE 17                                                         ______________________________________                                         Exam-  Starting alkyl                                                                               Product 16,16-dimethyl or                                 ple    ester of      17,17-dimethyl-9-oxo-15-                                         Example                                                                 hydroxy-13-trans-proste-                                                                            noic acid                                                 ______________________________________                                         1032   1006          9-oxo-15-hydroxy-16,16-dimethyl-13-trans-prostenoic                            acid                                                      1033   1007          9-oxo-15-hydroxy-16,16-dimethyl-7a,7b-bishomo-13-tran                          s-prostenoic acid                                         1034   1008          9-oxo-15-hydroxy-16,16-dimethyl-2-ethyl-13-trans-pros                          tenoic acid                                               1035   1009          9-oxo-15-hydroxy-16,16-dimethyl-3,3-dimethyl-13-trans                          -prostenoic acid                                          1036   1010          9-oxo-15-hydroxy-16,16-dimethyl-3-oxa-13-trans-proste                          noic acid                                                 1037   1011          9-oxo-15-hydroxy-16,16-dimethyl-7-nor-13-trans-proste                          noic acid                                                 1038   1012          9-oxo-15-hydroxy-16,16-dimethyl-2-fluoro-13-trans-pro                          stenoic acid                                              1039   1014          9-oxo-15-hydroxy-16,16-dimethyl-2-methyl-13-trans-pro                          stenoic acid                                              1040   1015          9-oxo-15-hydroxy-16,16-dimethyl-10a-homo-13-trans-pro                          stenoic acid                                              1041   1016          9-oxo-15-hydroxy-16,16-dimethyl-3-thia-13-trans-prost                          enoic acid                                                1042   1017          9-oxo-15-hydroxy-16,16-dimethyl-5-cis,13-trans-prosta                          dienoic acid                                              1043   1018          9-oxo-15-hydroxy-16,16-dimethyl-2-phenyl-13-trans-pro                          stenoic acid                                              1044   1019          9-oxo-15-hydroxy-17,17-dimethyl-13-trans-prostenoic                            acid                                                      1045   1020          9-oxo-15-hydroxy-17,17-dimethyl-7a,7b-bishomo-13-tran                          s-prostenoic acid                                         1046   1021          9-oxo-15-hydroxy-17,17-dimethyl-2-ethyl-13-trans-pros                          tenoic acid                                               1047   1022          9-oxo-15-hydroxy-17,17-dimethyl-3,3-dimethyl-13-trans                          -prostenoic acid                                          1048   1023          9-oxo-15-hydroxy-17,17-dimethyl-3-oxa-13-trans-proste                          noic acid                                                 1049   1024          9-oxo-15-hydroxy-17,17-dimethyl-7-nor-13-trans-proste                          noic acid                                                 1050   1025          9-oxo-15-hydroxy-17,17-dimethyl-2-fluoro-13-trans-pro                          stenoic acid                                              1051   1027          9-oxo-15-hydroxy-17,17-dimethyl-2-methyl-13-trans-pro                          stenoic acid                                              1052   1028          9-oxo-15-hydroxy-17,17-dimethyl-10a-homo-13-trans-pro                          stenoic acid                                              1053   1029          9-oxo-15-hydroxy-17,17-dimethyl-3-thia-13-trans-prost                          enoic acid                                                1054   1030          9-oxo-15-hydroxy-17,17-dimethyl-5-cis,13-trans-prosta                          dienoic acid                                              1055   1031          9-oxo-15-hydroxy-17,17-dimethyl-2-phenyl-13-trans-pro                          stenoiic acid                                             ______________________________________                                    

EXAMPLES 1056-1081

Treatment of the 9-oxo- acids and esters of Table 18 below with lithium perhydro-9b-boraphenalyl hydride by the procedure of Example 737 provides the 9α, 15-dihydroxy-16,16-dimethyl or 17,17-dimethyl-13-trans-prostenoic acid of the Table.

                  TABLE 18                                                         ______________________________________                                         Exam-  Starting 9-oxo                                                                               Product 9α-15-Dihydroxy-16,-                        ple    derivative of 16-dimethyl or 17,17-di-                                         Example       methyl-13-trans-prostenoic                                                     acids or esters                                           ______________________________________                                         1056   1032          9α,15-dihydroxy-16,16-dimethyl-13-trans-prosten                          oic acid                                                  1057   1033          9α,15-dihydroxy-16,16-dimethyl-7a,7b-bishomo-13                          -trans-prostenoic acid                                    1058   1034          9α,15-dihydroxy-16,16-dimethyl-2-ethyl-13-trans                          -prostenoic acid                                          1059   1035          9α,15-dihydroxy-16,16-dimethyl-3,3-dimethyl-13-                          trans-prostenoic acid                                     1060   1036          9α,15-dihydroxy-16,16-dimethyl-3-oxa-13-trans-p                          rostenoic acid                                            1061   1037          9α,15-dihydroxy-16,16-dimethyl-7-nor-13-trans-p                          rostenoic acid                                            1062   1038          9α,15-dihydroxy-16,16-dimethyl-2-fluoro-13-tran                          s-prostenoic acid                                         1063   1013          n-decyl 9α,15-dihydroxy-16,16-dimethyl-13-trans                          -prostenoate                                              1064   1039          9α,15-dihydroxy-16,16-dimethyl-2-methyl-13-tran                          sprostenoic acid                                          1065   1040          9α,15-dihydroxy-16,16-dimethyl-10a-homo-13-tran                          s-prostenoic acid                                         1066   1041          9α,15-dihydroxy-16,16-dimethyl-3-thia-13-trans-                          prostenoic acid                                           1067   1042          9α,15-dihydroxy-16,16-dimethyl-5-cis,13-trans-p                          rostadienoic acid                                         1068   1043          9α,15-dihydroxy-16,16-dimethyl-2-phenyl-13-tran                          s-prostenoic acid                                         1069   1044          9α,15-dihydroxy-17,17-dimethyl-13-trans-prosten                          oic acid                                                  1070   1045          9α,15-dihydroxy-17,17-dimethyl-7a,7b-bishomo-13                          -trans-prostenoic acid                                    1071   1046          9α,15-dihydroxy-17,17-methyl-2-ethyl-13-trans-p                          rostenoic acid                                            1072   1047          9α,15-dihydroxy-17,17-dimethyl-3,3-dimethyl-13-                          trans-prostenoic acid                                     1073   1048          9α,15-dihydroxy-17,17-dimethyl-3-oxa-13-trans-p                          rostenoic acid                                            1074   1049          9α,15-dihydroxy-17,17-dimethyl-7-nor-13-trans-p                          rostenoic acid                                            1075   1050          9α,15-dihydroxy-17,17-dimethyl-2-fluoro-13-tran                          s-prostenoic acid                                         1076   1026          n-decyl 9α,15-dihydroxy-17,17-dimethyl-13-trans                          -prostenoate                                              1077   1051          9α,15-dihydroxy-17,17-dimethyl-2-methyl-13-tran                          s-prostenoic acid                                         1078   1052          9α,15-dihydroxy-17,17-dimethyl-10a-homo-13-tran                          s-prostenoic acid                                         1079   1053          9α,15-dihydroxy-17,17-dimethyl-3-thia-13-trans-                          prostenoic acid                                           1080   1054          9α,15-dihydroxy-17,17-dimethyl                                           5-cis,13-trans-prostadienoic acid                         1081   1055          9α,15-dihydroxy-17,17-dimethyl-2-phenyl-13-tran                          s-prostenoic acid                                         ______________________________________                                    

EXAMPLE 1082

A solution of methyl 9-oxo-15-hydroxy-5-cis, 13-trans,17-cis-prostatrienoate (Example 374) in tetrahydrofuran is added to 1.1 equivalent of lithium perhydro-9b-boraphenyalyl hydride in tetrahydrofuran at -78°C. After 30 minutes equal volumes of 5% aqueous sodium carbonate and 30% aqueous hydrogen peroxide is added, and the solution is stirred 15 minutes. The solution is diluted with water and extracted with ether. The organic phase is dried (magnesium sulfate) and concentrated in vacuo to give methyl 9α,15α-dihydroxy-5-cis,13-trans,17-cis-prostatrienoate, contaminated with methyl 9β,15α-dihydroxy-5cis,13trans,17cis-prostatienoate. The crude mixture of esters is dissolved in methylene chloride and added to a refluxing solution of 1.2 equivalents of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in methylene chloride. After 5 hours, the solution is cooled and filtered. The filtrate is diluted with two volumes of ether, extracted with 5% aqueous sodium carbonate and dried with magnesium sulfate. The solution is concentrated in vacuo to give methyl 9α -hydroxy-15-oxo-5cis13-trans, 17cis-prostatrienoate and 9β-hydroxy-15-oxo-5cis, 13trans,17cis-prostatrienoate. The crude material is dissolved in benzene and 1.2 equivalents each of triethylamine and trimethylsilyl chloride is added. The triethylamine hydrochloride is removed by filtration and the solution is concentrated in vacuo to give methyl 9α-trimethylsiloxy-15-keto-5cis,13trans,17cis-prostatrienoate and the corresponding 9β-trimethylsiloxy derivative.

The siloxy derivatives are dissolved in ether at 0°C. and 1.05 equivalents of methyl magnesium bromide in ether is added. After the reaction is complete, the solution is poured into saturated aqueous ammonium chloride and extracted with ether. The ether is dried and concentrated in vacuo to give methyl 9α-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13-trans,17cis-prostatrienoate, and methyl 9α-trimethylsiloxy-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate, methyl 9β-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate, and methyl 9β-trimethylsiloxy-15β-hydroxy-15α-methyl 5cis,13trans,17-'cis-prostatrienoate. Hydrolysis of the siloxy functions of each in a solution of methanol, water and acetic acid (approximately 10:1:1, 3 hours ambient temperatures) and gives methyl 9α,15α-dihydroxy-15β-methyl-5cis-13trans,17cis-prostatrienoate, methyl 9α,15β-dihydroxy-15α-methyl-5cis,13trans, 17cis-prostatrienoate, methyl 9β,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate and methyl 9β,15β-dihydroxy-15α-methyl-5-cis,13trans,17cis-prostatrienoate separated by dry column chromatography and further purified by partition chromatography saponification (method of Example 122) of each component in 50% aqueous methanol with potassium hydroxide gives the corresponding free acids.

Treatment of a solution of methyl 9α,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate in methylene chloride with Collins reagent (CrO₃ -pyridine in methylene chloride) gives methyl 9-oxo-15α-hydroxy-15β-methyl-5cis,13-trans,17cis-prostatrienoate, saponification of which (method of Example 122) gives 9-oxo-15α-hydroxy-15β-methyl-5cis,13trans, 17cis-prostatrienoate acid.

Similar treatment of the 15β-hydroxy esters gives methyl 9-oxo-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate which gives 9-oxo-15β-hydroxy-15α-methyl5cis,13trans,17cis-prostatrienoic acid after saponification.

EXAMPLES 1083-1101

Treatment of the 9-oxo-15-hydroxy prostenoic esters of Table 18A below by the sequence of reactions described in Example 1082 is productive of the 9α,15-dihydroxy-15-methyl and the 9-oxo-15-hydroxy-15-methyl products of the table. Also prepared in the course of these reaction sequences are the ethyl (methyl for Example 1101) esters corresponding to the products of the table, the 9β-hydroxy derivatives corresponding to the listed 9α-hydroxy derivatives and their ethyl esters, the 15-keto derivatives of the 9α- and 9β-hydroxy compounds corresponding to the 9-oxo starting compounds, and the 9α- or 9β-trimethyl-silyloxy ethyl esters of the 15-keto and 15-hydroxy-15methyl compounds. In all cases both the 15α-hydroxy-15β-methyl and the 15β-hydroxy-15α-methyl products and intermediates are obtained. These epimers are separable by chromatographic procedures.

                  TABLE 18A                                                        ______________________________________                                                Starting 9-oxo-                                                         Ex-                                                                            15-hydroxy-ester                                                                      Product 15-hydroxy-                                                     ample  of Example                                                              15-methyl derivative                                                           ______________________________________                                         1083   260           9-oxo-15-methyl-15-                                       hydroxy-2-ethyl-13-                                                            trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-2-ethyl-13-                                                          trans-prostenoic acid                                                          1084   261           9-oxo-15-hydroxy-15-                                      methyl-3,3-dimethyl-                                                           13-trans-prostenoic                                                                                 acid and 9α,15-di-                                  hydroxy-15-methyl-                                                             3,3-dimethyl-13-trans-                                                         prostenoic acid                                                                1085   262           9-oxo-15-hydroxy-15-                                      methyl-3-oxa-13-trans-                                                                              prostenoic acid and                                                            9α,15-dihydroxy-15-                                                      methyl-3-oxa-13-trans-                                    prostenoic acid                                                                1086   264           9-oxo-15-hydroxy-15-                                      methyl-2-fluoro-13-                                                            trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-2-fluoro-                                                            13-trans-prostenoic                                                                                 acid                                                      1087   266           9-oxo-15-hydroxy-15-                                      methyl-2-phenyl-13-                                                            trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-2-phenyl-                                                            13-trans-prostenoic                                                                                 acid                                                      1088   267           9-oxo-15-hydroxy-15-                                                           methyl-2-methyl-13-                                       trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-2-methyl-                                                            13-trans-prostenoic                                                                                 acid                                                      1089   268           9-oxo-15-hydroxy-15-                                                           methyl-10a-homo-13-                                       trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-10a-homo-                                                            13-trans-prostenoic                                                                                 acid                                                      1090   272           9-oxo-15-hydroxy-15-                                      methyl-3-thia-13-                                                              trans-prostenoic acid                                                                               and 9α,15-dihydroxy-                                15-methyl-3-thia-13-                                                           trans-prostenoic acid                                                          1091   362           9-oxo-15-hydroxy-15-                                      methyl-3-thia-20-                                                              methyl-13-trans-pro-                                                                                stenoic acid and 9α,15-                             dihydroxy-15-methyl-3-                                                         thia-20-methyl-13-                                                             trans-prostenoic acid                                                          1092   343           9-oxo-15-hydroxy-15-                                      methyl-2,20-dimethyl-                                                          13-trans-prostenoic                                                                                 acid and 9α,15-di-                                  hydroxy-15-methyl-                                                             2,20-dimethyl-13-                                                              trans, prostenoic acid                                                         1093   323           9-oxo-15-hydroxy-15-                                                           methyl-3-oxa-20-methyl-                                   13-trans-prostenoic                                                                                 acid and 9α,15-di-                                  hydroxy-15-methyl-3-                                                           oxa-20-methyl-13-                                                              trans-prostenoic acid                                                          1094   284           9-oxo-15-hydroxy-15-                                      methyl-13-trans, 17-                                                           cis-prostadienoic acid                                                                              and 9α,15-dihydroxy-15-                             methyl-13-trans,17- -                                                          cis-prostadienoic acid                                                         1095   287           9-oxo-15-hydroxy-15-                                      methyl-7a, 7b-bishomo-                                                         13-trans, 17-cis-pro-                                                                               stadienoic acid and 9a,                                                        15-dihydroxy-15-methyl-                                                        7a, 7b-bishomo-13-                                        trans, 17-cis-prosta-                                                                               dienoic acid                                              1096   290           9-oxo-15-hydroxy-15-                                      methyl-3-oxa-13-trans,                                                                              17-cis-prostadienoic                                                           acid and 9a,15-dihydro-                                                        xy-15-methyl-3-oxa-13-                                    trans, 17-cis-prosta-                                                                               dienoic acid                                              1097   291           9-oxo-15-hydroxy-15-                                      methyl-7-nor-13-trans,                                                                              17-cis-prostadienoic                                                           acid and 9α, 15-di-                                                      hydroxy-15-methyl-7-                                      nor-13-trans, 17-cis-                                                          prostadienoic acid                                                             1098   292           9-oxo-15-hydroxy-15-                                      methyl-2-fluoro-13-                                                            trans, 17-cis-prosta-                                                                               dienoic acid and 9α,                                                     15-dihydroxy-15-methyl-                                   2-fluoro-13-trans,                                                             17-cis-prostadienoic                                                                                acid                                                      1099   293           9-oxo-15-hydroxy-15-                                      methyl-7a-homo-13-                                                             trans, 17-cis-prosta-                                                                               dienoic acid and 9α, 15-                            dihydorxy-15-methyl-7a-                                                        homo-13-trans, 17-cis-                                                         prostadienoic acid                                                             1100   300           9-oxo-15-hydroxy-15-                                      methyl-3-thia-13-trans,                                                                             17-cis-prostadienoic                                                           acid and 9α,15-di-                                                       hydroxy-15-methyl-3-                                      thia-13-trans, 17-cis-                                                         prostadienoic acid                                                             1101   733           9-oxo-15-hydroxy-15-                                      methyl-13-cis, 17-cis-                                                         prostadienoic acid and -                                                                            9α,15-dihydroxy-15-                                 methyl-13-cis, 17-cis                                                          prostadienoic acid                                                                    *methyl 15-hy-                                                                 droxy-9-oxo-                                                            13-cis-prost-                                                                         enoate only                                                             ______________________________________                                    

EXAMPLES 1102-1104

Hydrogenation of the 13-trans-prostenoic acids listed in Table 19 below by the procedure described in Example 699 is productive of the product prostanoic acids of the table. The product epimers are separable by chromatographic procedures.

                  TABLE 19                                                         ______________________________________                                               Starting 15-hy-                                                          droxy-15-methyl-                                                                     Product 15-hydroxy-                                                      Ex-                                                                            13-trans-pros-                                                                 15-methyl-prostanoic                                                           ample                                                                          tenoic acid                                                                          acid                                                                     ______________________________________                                         1102  9-oxo-15-hydroxy-                                                                             9-oxo-15-hydroxy-15-                                      15-methyl-3-oxa-                                                               methyl-3-oxa-prostanoic                                                        13-trans-pros-                                                                       acid                                                                     tenoic acid                                                                          (Example 1085)                                                           1103  9α,15-dihydroxy-                                                                        9α,15-dihydroxy-15-                                 15-methyl-3-oxa-                                                               methyl-3-oxa-pros-                                                             13-trans-pros-                                                                 tanoic acid                                                                          tenoic acid                                                                    (Example 1085)                                                           1104  9-oxo-15-hydroxy-                                                                             9-oxo-15-hydroxy-15-                                      15-methyl-10a-                                                                 methyl-10a-homo-pros-                                                          homo-13-trans-                                                                 tanoic acid                                                                    prostenoic acid                                                                      (Example 1089)                                                           ______________________________________                                    

EXAMPLE 1105 Preparation of all cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxido-cyclopentanol

A solution of 1.42 g. (10.0 moles) of all-cis-5hydroxy-2,3-oxidocyclopentylacetaldehyde- -lactol (E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 5ml. of DMSO is added to a stirred solution with the Whttig reagent [E. J. Corey et al. JACS, 91 5675 (1969)] also Example 1108 prepared from 13.3 g. (30 moles) of 4-carboxybutyltriphenylphosphonium bromide 2.52 g. (60 moles) of 57% sodium hydride dispersion, and 70 ml. of DMSO at 16°C. during 1 minute.

The solution is stirred at ambient temperature for 20 hours and poured into a stirred mixture of methylene chloride, ice, and hydrochloric acid. The organic phase is separated, and the aqueous phase is extracted with methylene chloride, saturated with sodium chloride, and extracted with ether. The combined organic extracts are partitioned with sodium bicarbonate. The aqueous basic extract is acidified with dilute HCl, saturated with sodium chloride, and extracted with ethyl acetate. The extract is washed with brine, dried over magnesium sulfate, and concentrated to give the crude title compound as an orange oil.

EXAMPLE 1106 Preparation of all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

To a stirred solution of ca. 1:6 moles of crude all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example 1105) in 1.6 ml. of ether is added 1.6 ml. of 4.0 N chromic acid in 4N sulfuric acid at 0°C. during 9 minutes. After stirring for 5 minutes at 0°C. the solution is diluted with brine, ether, and ethyl acetate. The organic phase is treated with isopropanol, washed with brine and dried over magnesium sulfate. Evaporation of the solvent gives the subject compound as an oil

EXAMPLE 1107 Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of 1.0 mmole of all-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example 1106) and 3.0 mmoles of sodium carbonate in 15 ml. of water is allowed to stand at room temperature for 3 hours. The solution is acidified with HCl, saturated with sodium chloride, and extracted with ether. The extract is washed with brine, dried over magnesium sulfate, and concentrated to give a mixture of the title compound and the isomeric compound, 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one. Further treatment of this mixture with N-10 sodium hydroxide at room temperature for 30 minutes causes the rearrangement of the latter isomer to the title compound, which is isolated from basic solution as above.

EXAMPLE 1107a Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

Treatment of cis-anti-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (E. J. Corey and R. Noyori Tetrahedron Letters, 1970, 311) with 4-carboxybutyltriphenylphosphonium bromide as described in Example 1105 is productive of 2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentan-1.alpha.-ol which on on oxidition by the method of Example 1106 provides 2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentanone, which in time on treatment with aqueous base by the procedure of Example 1107 furnishes the subject compound.

EXAMPLE 1108 Preparation of 4-carboxybutyltriphenylphosphonium bromide

A mixture of 103 g. of 5-bromovalevic acid and 152 g. of triphenylphosphine in 400 ml. of acetonitrile is refluxed for 48 hours, cooled, diluted with 100 ml. of benzene and allowed to crystallize. The crystals are filtered, washed with benzene and ether, to yield colorless material, m.p. 207°-209°C.

EXAMPLES 1109-1111

Treatment of the indicated ω-bromoalkanoic acids of Table 20 below with triphenylphosphine by the method described in Example 1108 produces the phosphonium bromides of the table.

                  TABLE 20                                                         ______________________________________                                         Ex-   Starting Φ-bromo-                                                                         Product                                                   ample alkanone acid  Phosphonium bromide                                       ______________________________________                                         1109  4-bromo-n-butyric                                                                             3-carboxypropyltri-                                             acid           phenylphosphonium                                                              bromide                                                   1110  6-bromo-n-hexanoic                                                                            5-carboxypentyltri-                                             acid           phenylphosphonium                                                              bromide                                                   1111  7-bromo-n-hepta-                                                                              6-carboxyhexyltri-                                              noic acid      phenylphosphonium                                                              bromide                                                   ______________________________________                                    

EXAMPLES 1112-1114

Treatment of all cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol with the Wittig reagent prepared from the indicated phosphonium bromides of Table 21 below, all by the procedure of Example 1105 is productive of the product compounds of the table.

                  TABLE 21                                                         ______________________________________                                         Ex-    Reagent phos- Product                                                   ample  phonium bromide                                                                              3,4-oxidocyclopentanol                                           of Example                                                              ______________________________________                                         1112   1109          all cis-2-(5-carboxy-2-cis-pentenyl)-3,4-oxidocyclope                          ntan-1-ol                                                 1113   1110          all cis-2-(7-carboxy-2-cis-heptenyl)-3,4-oxidocyclope                          ntan-1-ol                                                 1114   1111          all cis-2-(8-carboxy-2-cis-octenyl)-3,4-oxidocyclopen                          tan-1-ol                                                  ______________________________________                                    

EXAMPLES 1115-1117

Oxidation of the cyclopentanols indicated in Table 22 below by the method described in Example 1106 furnishes the corresponding product 3,4-oxidocyclopentanones of the table.

                  TABLE 22                                                         ______________________________________                                         Ex-   Starting cyclo-                                                                               Product                                                   ample pentan-1-ol of 3,4-oxidocyclopent-                                             Example        an-1-one                                                  ______________________________________                                         1115  1112           all cis-2-(5-carboxy-                                     2-cis-pentenyl)-3,4-                                                           oxidocyclopentan-1-                                                            one                                                                            1116  1113           all cis-2-(7-carboxy-                                     2-cis-heptenyl)-3,4-                                                           oxidocyclopentan-1-                                                            one                                                                            1117  1114           all cis-2-(8-carboxy-                                     2-cis-octenyl)-3,4-                                                            oxidocyclopentan-1-                                                            one                                                                            ______________________________________                                    

EXAMPLES 1118-1120

Alkaline treatment of the 3,4-oxidocyclopentanones of Table 23 below by the process described in Example 1107 is productive of the 4-hydroxycyclopentenones of the table.

                  TABLE 23                                                         ______________________________________                                         Ex-   Starting 3,4-  Product                                                   ample                                                                          oxidocyclo-                                                                          4-hydroxycyclo-                                                                pentanone of   pent-2-en-1-one                                                 Example                                                                  ______________________________________                                         1118  1115           2-(5-carboxy-2-                                           cis-pentenyl)-4-                                                               hydroxycyclo-                                                                                       pent-2-en-1-one                                           1119  1116           2-(7-carboxy-2-                                           cis-heptenyl)-                                                                                      4-hydroxycyclo-                                                                pent-2-en-1-one                                           1120  1117           2-(8-carboxy-2-                                           cis-octenyl)-4-                                                                hydroxycyclo-                                                                                       pent-2-en-1-one                                           ______________________________________                                    

EXAMPLES 1121-1124

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 24 below with dihydropyran (in the manner of Example 95) is productive of the corresponding bis-tetrahydropyranyl ether-ester of the table.

                  TABLE 24                                                         ______________________________________                                         Ex-    Starting 4-hy-                                                                               Product                                                   ample  droxycyclopent-                                                                              bis-tetrahydropyranyl                                     2-en-1-one of                                                                         ether-ester                                                                    Example                                                                 ______________________________________                                         1121   1107          4-tetrahydropyranyloxy-                                   2-(6-carbotetrahydro-                                                                               pyranyloxy-2-cis-hexenyl)                                                      cyclopent-2-en-1-one                                      1122   1118          4-tetrahydropyranyloxy-                                   2-(5-carbotetrahydro-                                                                               pyranyloxy-2-cis-pent-                                                         enyl)cyclopent-2-en-1-                                    one                                                                            1123   1119          4-tetrahydropyranyloxy-                                   2-(7-carbotetrahydro-                                                                               pyranyloxy-2-cis-heptenyl)-                                                    cyclopent-2-en-1-one                                      1124   1120          4-tetrahydropyranyloxy-                                   2-(8-carbotetrahydro-                                                                               pyranyloxy-2-cis-octenyl)-                                                     cyclopent-2-en-1-one                                      ______________________________________                                    

EXAMPLES 1125-1130

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 25 below with the indicated trialkylsilyl chloride by the method described in Example 958 is productive of the bis-trialkylsilyl ether-esters of the table.

                                      TABLE 25                                     __________________________________________________________________________          Starting 4-hydroxy-                                                       Example                                                                        cyclopentenone of                                                                   Trialkylsilyl-                                                                             Product                                                            Example     chloride                                                                               bis-trialkylsilyl ether-ester                         __________________________________________________________________________     1125 1107        (CH.sub.3).sub.3 SiCl                                                                  4-trimethylsiloxy-2-(6-carbotrimethyl-                                         siloxy-2-cis-hexenyl)cyclopent-2-en-1-one             1126 1118        (CH.sub.3).sub.3 SiCl                                                                  4-trimethylsiloxy-2-(5-carbotrimethyl-                                         siloxy-2-cis-pentenyl)cyclopent-2-en-1-one            1127 1119        (CH.sub.3).sub.3 SiCl                                                                  4-trimethylsiloxy-2-(7-carbotrimethyl-                                         siloxy-2-cis-heptenyl)cyclopent-2-en-1-one            1128 1120        (CH.sub.3).sub.3 SiCl                                                                  4-trimethylsiloxy-2-(8-carbotrimethyl-                                         siloxy-2-cis-octenyl)cyclopent-2-en-1-one             1130 1107        dimethyliso-                                                                           4-dimethylisopropylsiloxy-2-(6-carbodi-                                propyl silyl                                                                           methylisopropylsiloxy-2-cis-hexenyl)cyclo-                             chloride                                                                               pent-2-en-1-one                                       __________________________________________________________________________

EXAMPLE 1131 Preparation of 1-oxo-2-hydroxy-bicyclo[3.3.0]oct-4-ene

A solution of 6.2 g. (50 mole) of the lactone of cis-2-hydroxycyclopent-4-ene-1-acetic acid [P. A. Grieco, J. Org. Chem., 37, 2363 (1972)] in 350 ml. of toluene (dried over molecular sieves) is cooled to -75°C. and treated dropwise under nitrogen with 84 ml. 0.89 M diisobutyl aluminum hydride (10.55 g., 74 mole) over a period of about one hour maintaining the temperature at -74 + 2°C. The resulting clear solution is stirred at -75°C. for 2 hours and poured with stirring into a mixture of 15 ml. of concentrated hydrochloric acid and 300 ml. of ice water. The mixture is stirred while warming to room temperature. The layers are separated and the aqueous layer is treated with salt and extracted with three small portions of ether. The combined organic portions are dried over sodium sulfate and evaporated at reduced pressure (75°C. water bath) to yield the product (homogeneous by thin layer chromatography) as a pale yellow mobile liquid.

EXAMPLE 1132 Preparation of 1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene

A solution of the sodium salt dimethyl sulfoxide is prepared by stirring under nitrogen a mixture of 160 ml. dry dimethyl sulfoxide (dried over molecular sieves and a few pellets of calcium hydride) with 6.0 g. (0.25 mole) of sodium hydride (prepared by washing 10.5 g. of 57% sodium hydride dispersion in mineral oil with two 30 ml. portions of hexane.) The mixture is warmed with stirring at 75°C. (oil bath) for 2.5 hours.

This solution is added over about five minutes to a solution under nitrogen of 44 grams (0.1 mole) of 4-carboxybutyltriphenylphosphonium bromide (Example 1108) in 180 ml. of dry dimethyl sulfoxide. The resulting dark reddish brown solution is stirred for ten minutes, cooled to room temperature and treated with a solution of crude 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene (6.2 g., 50 mole) (Example 1131) in 20 ml. of anhydrous dimethyl sulfoxide. The resulting solution is stirred 16 hours and then treated with 250 ml. of ice water.

This brown solution is extracted with two portions of ether to remove neutral material then made strongly acidic with hydrochloric acid. The solution is extracted into four 100 ml. portions of methylene chloride. The combined methylene chloride extacts are washed with water, then extracted with four 100 ml. portions of 5% sodium bicarbonate. The combined aqueous extracts are washed with methylene chloride and made acidic to Congo Red with concentrated hydrochloric acid. The mixture is extracted with three 100 ml. portions of methylene chloride. The organic extracts are combined, dried over sodium sulfate and the solvent is evaporated at reduced pressure. The residue (an oily solid) is extracted several times with ether and the ethereal extracts are combined and evaporated at reduced pressure to yield the crude product as a dark oil. The product is purified by chromatograph6 on silica gel, eluting with ether. The product is a colorless liquid.

EXAMPLE 1133 Preparation of 2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one

A solution of 3.2 g. (0.5 mole) of 1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene (Example 1132) in 60 ml. of reagent acetone is treated dropwise with a total of 6 ml. of 8N chromic acid in sulfuric acid at 0°C. The oxidation is rather slow. The resulting mixture is dissolved in 200 ml. of water and the solution is extracted with six 50 ml. portions of ether. The combined ethereal extracts are dried over sodium sulfate and the solvent is evaporated at reduced pressure to yield the product as a yellow oil.

EXAMPLE 1134 Preparation of 2-(6-carboxy-2-cis-hexenyl(cyclopent-2-en-1-one

A solution of 3 g. of crude 2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one (Example 1133) in 100 ml. of 2% sodium hydroxide is stirred at 80°C. under nitrogen for 1.5 hours. The cooled solution is acidified to Congo Red and extracted into ether. The ethereal extracts are dried over sodium sulfate and evaporated at reduced pressure to afford the product.

EXAMPLES 1135-1137 Treetment of 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene by the procedure described in Example 1132 with the ylids derived from the phosphonium bromides listed in Table 26 below furnishes the product 1-hydroxy-cyclopent-3-enes of the table.

                  TABLE 26                                                         ______________________________________                                         Ex-    Starting phos-                                                                               Product                                                   ample  phonium bromide                                                                              1-hydroxy-2-(ω-carboxy-                                    of Example                                                              2-cis-alkenyl)cyclopent-                                                       3-enes                                                                         ______________________________________                                         1135   1109          1-hydroxy-2-(5-carboxy-                                   2-cis-pentenyl)cyclo-                                                                               pent-3-ene                                                1136   1110          1-hydroxy-2-(7-carboxy-                                   2-cis-heptenyl)cyclo-                                                                               pent-3-ene                                                1137   1111          1-hydroxy-2-(8-carboxy-                                   2-cis-octenyl)cyclo-                                                                                pent-3-ene                                                ______________________________________                                    

EXAMPLES 1138-1140

Oxidation of the 1-hydroxycyclopent-3-enes listed in Table 27 below by the procedure described in Example 1133 is productive of the product cyclopent-3-en-1-ones of the table.

                  TABLE 27                                                         ______________________________________                                         Ex-    Starting 1-   Product                                                   ample                                                                          hydroxycyclo-                                                                         2-(ω-carboxy-2-cis-                                                      pent-3-ene of                                                           alkenyl)cyclopent-3-                                                                  Example                                                                 en-1-one                                                                       ______________________________________                                         1138   1135          2-(5-carboxy-2-cis-                                       pentenyl)cyclopent-3-                                                          en-1-one                                                                       1139   1136          2-(7-carboxy-2-cis-                                       heptenyl)cyclopent-3-                                                          en-1-one                                                                       1140   1137          2-(8-carboxy-2-cis-                                       octenyl)cyclopent-3-                                                           en-1-one                                                                       ______________________________________                                    

EXAMPLES 1141-1143

Base treatment according to the procedure described in Example 1134 of the cyclopent-3-ene-1-ones listed in Table 28 below is productive of the product cyclopent-2-en-1-ones of the table.

                  TABLE 28                                                         ______________________________________                                         Ex-   Starting 2-(ω-                                                                          Product                                                   ample                                                                          carboxy-2-cis-                                                                       2-(ω-carboxy-2-cis-                                                alkenyl)cyclo-                                                                 alkenyl)cyclopent-                                                                   pent-3-ene-1-                                                            2-en-1-one                                                                           one of Example                                                           ______________________________________                                         1141  1138           2-(5-carboxy-2-cis-                                       pentyl)cyclopent-                                                              2-en-1-one                                                                     1142  1139           2-(7-carboxy-2-cis-                                       heptenyl)cyclopent-                                                            2-en-1-one                                                                     1143  1140           2-(8-carboxy-2-cis-                                       octenyl)cyclopent-                                                             en-en-1-one                                                                    ______________________________________                                    

EXAMPLES 1144-1146

Treatment of the listed 2-(ω-carboxy-2-cis-alkenyl)cyclopent-2-en-1-one of Table 29 below with diazomethane in the usual manner is productive of the product methyl esters of the table.

                  TABLE 29                                                         ______________________________________                                         Ex-   Starting car-  Product                                                   ample boxylic acid   2-(ω-carbomethoxy-2-cis-                                  of Example                                                               alkenyl)cyclopent-2-en-                                                        1-one                                                                          ______________________________________                                         1144  1141           2-(5-carbomethoxy-2-cis-                                  pentenyl)cyclopent-2-en-                                                       1-one                                                                          1145  1142           2-(7-carbomethoxy-2-cis-                                  heptenyl)cyclopent-2-en-                                                       1-one                                                                          1146  1143           2-(8-carbomethoxy-2-cis-                                  octenyl)cyclopent-2-en-                                                        1-one                                                                          ______________________________________                                    

EXAMPLES 1147-1149

Treatment by the procedure of Example 120 of the cyclopentenones listed in Table 30 below with lithium diisobutylmethyl-(3-triphenylmethoxy-1-trans-5-cis-octadienyl) alanate, also prepared by the procedure of Example 120 from 3-triphenylmethoxy-cis-5-en-octyne-1 (Example 139), diisobutylaluminum hydride and methyl lithium, followed by hydrolysis of the intermediate 15-triphenylmethoxy derivatives by treatment with acetic acid-tetrahydrofuran-water (4:2:1) in the manner of Example 121, and then by saponification of the intermediate methyl esters by the process described in Example 122 is productive of the product prostatrienoic acids of the table.

                  TABLE 30                                                         ______________________________________                                         Ex-   Starting 2-(ω-                                                                          Product                                                   ample                                                                          carbomethoxy-2-                                                                      9-oxo-15-hydroxy-5-                                                      cis-alkenyl)-                                                                        cis, 13-trans,17-cis-                                                          cyclopent-2-en-                                                          prostatrienoic acids                                                           1-one of Example                                                               ______________________________________                                         1147  1144           9-oxo-4-nor-15-hydroxy-                                   5-cis-13-trans-17-                                                             cis-prostatrienoic                                                                                  acid                                                      1148  1145           9-oxo-4a-homo-15-hydro-                                                        xy-5-cis-13-trans-17-                                     cis-prostatrienoic                                                                                  acid                                                      1149  1146           9-oxo-4a-bishomo-15-hy-                                                        droxy-5-cis-13-trans-                                     17-cis-prostatrienoic                                                                               acid                                                      ______________________________________                                    

EXAMPLES 1150-1159

Treatment of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listed in Table 31 below with lithium trimethyl[3-(p-anisyldiphenylmethoxy)-grans-1-octenyl] according to the procedure described in Example 960 is productive of the 9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadienoic acids of the table as well as of the corresponding 15-epi derivatives, separable from the listed 15-normal derivatives by chromatography.

                  TABLE 31                                                         ______________________________________                                         Ex-   Starting blocked                                                         ample 4-oxycyclopent-                                                                               9-oxo-11α,15-dihydroxy-                             2-en-1-one of                                                                  5-cis,13-trans-pros-                                                                 Example        tadienoic acids                                           ______________________________________                                         1150  1121           9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadie                          noic acid (prostaglandin E.sub.2)                         1151  1125           9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadie                          noic acid (prostaglandin E.sub.2)                         1152  1130           9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadie                          noic acid (prostaglandin E.sub.2)                         1153  1122           9-oxo-11α,15-dihydroxy-4-nor-5-cis,13-trans-pro                          stadienoic acid                                           1154  1126           9-oxo-11α,15-dihydroxy-4-nor-5-cis,13-trans-pro                          stadienoic acid                                           1155  1123           9-oxo-11α,15-dihydroxy-4a-homo-5-cis,13-trans-p                          rostadienoic acid                                         1156  1127           9-oxo-11α,15-dihydroxy-4a-homo-5-cis,13-trans-p                          rostadienoic acid                                         1158  1124           9-oxo-11α,15-dihydroxy-4a,4b-homo-5-cis,13-tran                          s-prostadienoic acid                                      1159  1128           9-oxo-11α,15-dihydroxy-4a,4b-homo-5-cis,13-tran                          s-prostadienoic acid                                      ______________________________________                                    

EXAMPLES 1160-1169

Treatment by the procedure described in Example 123 of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listed in Table 32 below with lithium diisobutylmethyl(3-triphenylmethoxy-1-trans-5-cis-octadienyl)alanate, prepared from 3-triphenylmethoxy-cis-5-en-octyne-1- (Example 139) by the procedure of Example 120, followed by the cleavage of blocking groups and isolation of products by the method described in Example 124 is productive of the 9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-prostatrienoic acids of the table; also formed are the corresponding 15-epi derivatives which are separable by chromatography from the listed 15-normal derivatives.

                  TABLE 32                                                         ______________________________________                                               Starting blocked                                                                              Product                                                   Ex-   4-oxycyclopent-                                                                               9-oxo-11α,15-dihydroxy-                             ample                                                                          2-en-1-one of                                                                  5-cis,13-trans,17-cis-                                                               Example                                                                  prostatrienoic acids                                                           ______________________________________                                         1160  1121           9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-pr                          ostatrienoic acid (prostaglandin E.sub.3)                 1161  1125           9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-pr                          ostatrienoic acid (prostaglandin E.sub.3)                 1162  1130           9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-pr                          ostatrienoic acid (prostaglandin E.sub.3)                 1163  1122           9-oxo-11α,15-dihydroxy-4-nor-5-cis,13-trans,17-                          cis-prostatrienoic acid                                   1164  1126           9-oxo-11α,15-dihydroxy-4-nor-5-cis,13-trans,17-                          cis-prostatrienoic acid                                   1165  1123           9-oxo-11α,15-dihydroxy-4a-homo-5-cis,13-trans,1                          7-cis-prostatrienoic acid                                 1166  1127           9-oxo-11α,15-dihydroxy-4a-homo-5-cis,13-trans,1                          7-cis-prostatrienoic acid                                 1168  1124           9-oxo-11α,15-dihydroxy-4a,4b-bishomo-5-cis,                              13-trans,17-cis-prostatrienoic acid                       1169  1128           9-oxo-11α,15-dihydroxy-4a,4b-bishomo-5-cis-13-t                          rans,17-cis-prostatrienoic acid                           ______________________________________                                    

EXAMPLE 1170 Preparation of 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoic acid

Treatment in the manner described in Example 733 of 4-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxy-2-cis-hexenyl)cyclopent-2-en-1-one (Example 1121) with the Grignard reagent prepared from magnesium and 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) also as described in Example 733 in the presence of cuprous iodide tri-n-butylphosphine complex is productive after chromatography of prostaglandin E₂ and 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoic acid.

EXAMPLES 1171 and 1172

Treatment of the two 9-oxo derivative listed in Table 33 below with lithium perhydro-9b-boraphenalylhydride in the manner described in Example 737 furnishes the indicated 9α,15-dihydroxy-13-cis-prostenoic acids.

                  TABLE 33                                                         ______________________________________                                         Ex-   Starting 9-oxo-                                                                               Product                                                   ample                                                                          derivative of                                                                        9α,15-dihydroxy-13-cis-                                                  Example                                                                  prostenoic acids                                                               ______________________________________                                         1171   736           9α,15-diohydroxy-13-cis-                            prostenoic acid                                                                1172  1170           9α,15-dihydroxy-5-cis                               prostadienoic acid                                                             ______________________________________                                    

EXAMPLE 1173 Preparation of 1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

To an ice cooled solution of 3.5 g. (50 moles) of 2-methyl-2-butene in 25 ml. of tetrahydrofuran under an inert atmosphere is added 25 ml. of 1 M diborane in tetrahydrofuran dropwise over 10 minutes. The mixture is stirred at 0°-5°C. for 2 hours and then the solvent is removed under vacuum. The residue is dissolved in 20 ml. of carbon tetrachloride and to the resulting solution cooled to 0°C. is added a solution of 5.25 g. (22 mole) of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995) in 10 ml. of carbon tetrachloride over 10 minutes. The cooling bath is removed and the mixture is allowed to stir at ambient temperature for 1.5 hours. The mixture is cooled to 0°C. and a solution of 3.52 g. (22 moles) of bromine in 15 ml. of carbon tetrachloride is added over 10 minutes. The cooling bath is removed and the mixture is refluxed for 6 hours under an inert atmosphere. The mixture is cooled and poured into dilute sodium hydroxide solution. The organic phase is washed with water and saturated brine, dried (Na₂ SO₄), and evaporated. The residue is chromatographed upon silica gel and the title compound is isolated with 5% ethyl acetate in benzene.

EXAMPLE 1174 Preparation of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol

A mixture of 3.19 g. (10 moles) of 1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example 1173) and 90 ml. of 3:1:1 tetrahydrofuran-acetic acid-water is stirred at amibent temperatures for 20 hours. The solvent is evaporated in vacuo and the residue is chromatographed on silica gel. The title compound is isolated using 10-20% ethyl acetate in benzene.

EXAMPLE 1175 Preparation of 1-bromo-4,4-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 1.88 g. (8 moles) of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8 moles) of triphenylmethyl bromide in 20 ml. of pyridine and purification of Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1176 Preparation of 1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

Treatment of 7.15 g. (30 moles) of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) with 33 moles of disiamylborane in carbon tetrachloride followed by 30 moles of bromide in carbon tetrachloride, refluxing the resulting mixture, and isolation by chromatography on silica gel, all as described in Example 1173 gives the title compound.

EXAMPLE 1177 Preparation of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol

Treatment of 7.35 g. (23 moles) of 1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example 1176) with 200 ml. of 3:1:1 tetrahydrofuran-acetic acid-water and purification on silica gel all as described in Example 1174 gives the title compound.

EXAMPLE 1178 Preparation of 1-bromo-5,5-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 3.53 g. (15 moles) of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol (Example 1177) with 4.85 g. (15 moles) of triphenylmethyl bromide in 35 ml. of pyridine and purification on Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1179 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

To a mixture of 0.650 g. (16.91 mole) of sodium borohydride and 3.17 g. (45.2 moles) of 2-methyl-2-butene in 40 ml. of diglyme cooled to -5°C. under an inert atmosphere is added over 15 minutes 3.24 g. (22.6 moles) of boron trifluoride ethereate and the resulting mixture is stirred at 0°C. for 2 hours. To this mixture is then added over 5 minutes 8.32 g. (22.6 moles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of diglyme, the cooling bath is removed, and the mixture is stirred at ambient temperatures for 1.5 hours. The mixture is cooled to 0°C. and 6.0 g. of finely divided anhydrous trimethylamine oxide is added over 10 minutes. The cooling bath is removed and the mixture is stirred at ambient temperatures for 0.5 hour. The mixture is then poured into 200 ml. of 15% sodium hydrooxide solution, a solution of 16 g. (63 moles) of iodine in 20 ml. of tetrahydrofuran is added immediately, and the resulting mixture is stirred for 0.5 hour. The organic phase is separated and the aqueous phase is washed with ether. The combined organic phase and washings are decolorized with 55 sodium thiosulfate solution, washed with saturated brine, dried (Na₂ SO₄), and evaporated. The residue is dry-columned chromatographed upon alumina using hexane as eluent and the title compound is isolated as an oil.

EXAMPLE 1180 Preparation of 3-triphenylmethoxy-cis-oct-5-en-1-yne

Treatment of 22 g. of cis-oct-5-en-1-yne-3-ol, prepared according to the procedure of J. Fried, C. H. Lin, J. C. Sih, P. Dalven, G. F. Cooper, J. Amer. Chem. Soc., 94, 4342 (1972), with 58 g. of triphenylmethyl bromide in 100 ml. of pyridine and purification on Florisil, all as described in Example 728 gives the title compound.

EXAMPLE 1181 Preparation of 1-iodo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 20 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne with 55 moles of disiamylborane in diglyme, followed by trimethylamine oxide, aqueous sodium hydroxide, and iodine, and purification of alumina, all as described in Example 1179, gives the title compound.

EXAMPLE 1182 Preparation of 1-bromo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 15 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne (Example 1180) with 41 moles of disiamylborane in tetrahydrofuran, replacing the solvent with carbontetrachloride, addition of 41 moles of bromine, and refluxing the mixture, all as described in Example 1173, and purification of the material upon Florisil as described in Example 728 gives the title compound.

EXAMPLE 1183 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) with disamylborane, trimethylamine oxide and iodine by the procedure described in Example 1179 is productive of the subject compound.

EXAMPLE 1184 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) with disiamylborane, trimethylamine oxide and iodine by the process described in Example 1179 is productive of the subject compound.

EXAMPLE 1185 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) with disiamylborane and the bromide by the procedure described in Example 1173 is productive of the title compound.

EXAMPLE 1186 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) with disiamylborane and the bromine by the procedure described in Example 1173 is productive of the title compound.

EXAMPLE 1187 Preparation of the Grignard reagent of 1-bromo-3-triphenylmethoxy-trans-1-octene at 33°C.

To a slurry of 0.585 g. (0.0241 g. atom) of magnesium and 5 ml. of tetrahydrofuran under an argon atmosphere is added 2 ml. of a solution of 7.536 (0.0168 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in 10 ml. of tetrahydrofuran. The mixture is warmed to 35°C. and reaction is initiated with 1 drop of methyl iodide. The reaction is allowed to exotherm to 37°C. and then to cool to 33°C. whereupon the remainder of the halide is added at a rate to maintain 33°C. After complete addition of the halide, the mixture is stirred at 33°C. for 1 hour and is separated from the excess magnesium to yield a tetrahydrofuran solution of the title Grignard reagent.

EXAMPLE 1188 Preparation of 11-deoxy-8β-methyl-prostaglandin E₁ methyl ester, 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester, methyl 15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate, and methyl 15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate

The Grignard reagent, prepared as described in Example 1187 from 0.585 g. of magnesium, 7.536 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 10 ml. of tetrahydrofuran, is added to an ice cooled solution of 3.76 g. of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) and 0.305 g. of copper (I) iodide-tri-n-butylphosphine complex in 10 ml. of tetrahydrofuran over 10 minutes under an inert atmosphere. The mixture is stirred with cooling for 0.5 hour and to it is then added 46 g. of methyl iodide. The cooling bath is removed and the mixture is stirred at ambient temperatures for 48 hours. The mixture is poured into saturated ammonium chloride solution and is extracted into ether. The organic phase is washed with saturated brine and is evaporated. The residue is heated to 80°C. with 100 ml. of 80% aqueous acetic acid for 0.5 hour and the mixture is then evaporated to dryness. The residue is dry-column chromatography upon silica gel using 4:1 benzene-ethyl acetate as eluent to afford a mixture of 11-deoxy-8β-methyl-prostaglandin E₁ methyl ester and 11-deoxy-8α-methyl- 8-iso-prostaglandin E₁ methyl ester and a mixture of methyl 15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate and methyl 15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate. Further separation of the 8β and 8α isomers is accomplished by a combination of partition chromatography and thin layer chromatography.

EXAMPLES 1190- 1205

Treatment by the procedure of Example 1188 of the cyclopentenones listed in Table 34 below with the Grignard reagent, prepared as described in Example 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyl iodide furnishes the product 8α and 8β methyl prostenoates of the table. The products are all obtained via the corresponding 15-O-triphenylmethyl derivatives, which are hydrolytically cleaved as described in Example 1188.

                                      TABLE 34                                     __________________________________________________________________________     Example                                                                             Starting cycloalkenene                                                                     Starting 1-bromo-3-                                                                        Product 8-alkyl prostenoates                           of Example                                                                triphenylmethoxy-1-                                                            trans-alkene of                                                                                 Example                                                       __________________________________________________________________________     1190 13          1175        ethyl 8-β-methyl-9-oxo-15-hydroxy-16,16-                                  dimethyl-13-trans-prostenoate                                                  ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-d                                  imethyl-8-iso-13-trans-prostenoate                                             ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-d                                  imethyl-13-cis-prostenoate                                                     ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                  dimethyl-8-iso-13-cis-prostenoate                 1191 13          1178        ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-d                                  imethyl-13-trans-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-8-iso-13-trans-prostenoate                                            ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-d                                  imethyl-13-cis-prostenoate                                                     ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-8-iso-13-cis-prostenoate                 1192 13          1182        ethyl 8β-methyl-9-oxo-15-hydroxy-13-tran                                  s, 17-cis-prostadienoate                                                       ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                  13-trans,17-cis-prostadienoate                                                 ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,                                   17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                  13-cis, 17-cis-prostadienoate                     1193 13          1185        ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                  l-13-trans-prostenoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                  yl-8-iso-13-trans-prostenoate                                                  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                  l-13-cis-prostenoate                                                           ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                  20-ethyl-13-cis-prostenoate                       1194 84          1186        decyl 8β-methyl-9-oxo-15-hydroxy-20-meth                                  yl-13-trans-prostenoate                                                        decyl 8α-methyl-9-oxo-15-hydroxy-20-met                                  hyl-8-iso-13-trans-prostenoate                                                 decyl 8β-methyl-9-oxo-15-hydroxy-20-meth                                  yl-13-cis-prostenoate                                                          decyl 8α-methyl-9-oxo-15-hydroxy-20-met                                  hyl-8-iso-13-cis-prostenoate                      1195 23          728         ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-b                                  ishomo-13-trans-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-8-iso-13-trans-prostenoate                                             ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-b                                  ishomo-13-cis-prostenoate                                                      ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-8-iso-13-cis-prostenoate                  1196 31          1185        ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bi                                  sethyl-13-trans-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-b                                  isethyl-8-iso-13-trans-prostenoate                                             ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bi                                  sethyl-13-cis-prostenoate                                                      ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-b                                  isethyl-8-iso-13-cis-prostenoate                  1197 46          1175        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                  6,16-dimethyl-13-trans-prostenoate                                             ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                  16,16-dimethyl-8-iso-13-trans-prostenoate                                      ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                  6,16-dimethyl-13-cis-prostenoate                                               ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                  16,16-dimethyl-8-iso-13-cis-prostenoate           1198 46          1182        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                  3-trans,17-cis-prostadienoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                  8-iso-13-trans,17-cis-prostadienoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-1                                  3-cis,17-cis-prostadienoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                  8-iso-13-cis,17-cis-prostadienoate                1199 53          1186        ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-2                                  0-methyl-13-trans-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                  20-methyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-2                                  0-methyl-13-cis-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                  20-methyl-8-iso-13-cis-prostenoate                1200 70          1178        ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluor                                  o-17,17-dimethyl-13-trans-prostenoate                                          ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluo                                  ro-17,17-dimethyl-8-iso-13-trans-prostenoate                                   ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluor                                  o-17,17-dimethyl-13-cis-prostenoate                                            ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluo                                  ro-17,17-dimethyl-8-iso-13-cis-prostenoate        1201 111         728         ethyl 8β-methyl-9-oxo-15-hydroxy-10a-hom                                  o-13-trans-prostenoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-10a-ho                                  mo-8-iso-13-trans-prostenoate                                                  ethyl 8β-methyl-9-oxo-15-hydroxy-10a-hom                                  o-13-cis-prostenoate                                                           ethyl 8α-methyl-9-oxo-15-hydroxy-10a-ho                                  mo-8-iso-13-cis-prostenoate                       1202 79          1186        ethyl 8β-methyl-9-oxo-15-hydroxy-2-pheny                                  l-20-methyl-13-trans-prostenoate                                               ethyl 8α-methyl-9-oxo-15-hydroxy-2-phen                                  yl-20-methyl-8-iso-13-trans-prostenoate                                        ethyl 8β-methyl-9-oxo-15-hydroxy-2-pheny                                  l-20-methyl-13-cis-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-2-phen                                  yl-20-methyl-8-iso-13-cis-prostenoate             1203 900         1182        methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-trans,17-cis-prostatrienoate                                                methyl 8α-methyl-9-oxo-15-hydroxy-8-iso                                  -5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-cis,17-cis-prostatrienoate                                                  methyl 8α-methyl-9-oxo-15-hydroxy-8-iso                                  -5-cis,13-cis,17-cis-prostatrienoate              1204 900         728         ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,1                                  3-trans-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                  5-cis,13-trans-prostadienoate                                                  ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,1                                  3-cis-prostadienoate                                                           ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                  5-cis,13-cis-prostadienoate                       1205 900         1185        ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                  l-5-cis,13-trans-prostadienoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                  yl-8-iso-5-cis,13-trans-prostadienoate                                         ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethy                                  l-5-cis,13-cis-prostadienoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-20-eth                                  yl-8-iso-5-cis,13-cis-prostadienoate              __________________________________________________________________________

EXAMPLES 1206-1273

Treatment of the designated 9-oxo-prostenoic acid and ester derivatives listed in Table 35 below with sodium borohydride in ethanol as described in Example 257 gives the product 9α and 9β hydroxy derivatives of the table, which are separable by standard chromatographic techniques.

                  TABLE 35                                                         ______________________________________                                         Ex-   Starting 9-oxo-                                                                               Product 9-hydroxy                                         ample derivative     derivatives                                               ______________________________________                                         1206  11-deoxy-8β-methyl-prostaglandin E.sub.1 methyl ester (Example            1188)          11-deoxy-8β-methyl-prostaglandin F.sub.1                                  α and F.sub.1 β methyl esters                  1207  11-deoxy-8α-methyl-8-iso-prostaglandin E.sub.1 methyl ester              (Example 1188) 11-deoxy-8α-methyl-8-iso-prostaglandin F.sub.1                           α and F.sub.1 β methyl esters                  1208  methyl 15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate (Example             1188)          methyl 9α/β ,15-dihydroxy-8β-methyl-1                          3-cis-prostenoates                                        1209  methyl 15-hydroxy-8α-methyl-9-oxo-13-cis-prostenoate (Example            1188)          methyl 9α/β ,15-dihydroxy                                           8α-methyl-8-iso-13-cis-prostenoates                 1210  ethyl 8β-methyl-9-oxo-15-hydroxy-16-16-dimethyl-13-trans-proste           noate (Example 1190)                                                                          ethyl 8β-methyl-9α/β,15-dihydroxy-16,                          16-dimethyl-13-trans-prostenoates                         1211  ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso-13-trans           -prostanoate (Example 1190)                                                                   ethyl 8α-methyl-9α/β,15-dihydroxy-16                          ,16-dimethyl-8-iso-13-trans-prostenoates                  1212  ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-13-cis-prosteno           ate (Example 1190                                                                             ethyl 8β-methyl-9α/β,15-dihydroxy-16,                          16-dimethyl-13-cis-prostenoates                           1213  ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso-13-cis-p           rostenoate (Example 1190)                                                                     ethyl 8α-methyl-9α/β,15-dihydroxy-16                          ,16-dimethyl-8-iso-13-cis-prostenoates                    1214  ethyl-8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-trans-proste           noate (Example 1191)                                                                          ethyl 8β-methyl-9α/β,15-dihydroxy-17,                          17-dimethyl-13-trans-prostenoates                         1215  ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso-13-trans           -prostenoate (Example 1191)                                                                   ethyl 8α-methyl-9α/β,15-dihydroxy-17                          ,17-dimethyl-8-iso-13-trans-prostenoates                  1216  ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-cis-prosteno           ate (Example 1191)                                                                            ethyl 8β-methyl-9α/β,15-dihydroxy-17,                          17-dimethyl-13-cis-prostenoates                           1217  ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso-13-cis-p           rostenoate (Example 1191)                                                                     ethyl 8α-methyl-9α/β,15-dihydroxy-17                          ,17-dimethyl-8-iso-13-cis-prostenoates                    1218  ethyl 8β-methyl-9-oxo-15-hydroxy-13-trans-17-cis-prostadienoate            (Example 1192)                                                                               ethyl 8β-methyl-9α/β,15-dihydroxy-13-                          trans,17-cis-prostadienoates                              1219  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-trans,17-cis-prostad           ienoate (Example 1192)                                                                        ethyl 8α-methyl-9α/β,15-dihydroxy-8-                          iso-13-trans 17-cis-prostadienoates                       1220  ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,-17-cis-prostadienoate            (Example 1192) ethyl 8β-methyl-9α/β,15-dihydroxy-13-                          cis,17-cis-prostadienoates                                1221  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-cis,17-cis-prostadie           noate (Example 1192)                                                                          ethyl 8α-methyl-9α/β,15-dihydroxy-8-                          iso-13-cis-17-cis-prostadienoates                         1222  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-trans-prostenoate            (Example 1193) ethyl 8β-methyl-9α/β,15-dihydroxy-20-                          ethyl-13-trans-prostenoates                               1223  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-trans-prost           enoate (Example 1193)                                                                         ethyl 8α-methyl-9α/β,15-dihydroxy-20                          -ethyl-8-iso-13-trans-prostenoates                        1224  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-cis-prostenoate              (Example 1193) ethyl 8β-methyl-9α/β,15-dihydroxy-20-                          ethyl-13-cis-prostenoates                                 1225  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-cis-prosten           oate (Example 1193)                                                                           ethyl 8α-methyl-9α/β,15-dihydroxy-20                          -ethyl-8-iso-13-cis-prostenoates                          1226  decyl 8β-methyl-9-oxo-15-hydroxy-20-methyl-13-trans-prostenoate            (Example 1194)                                                                               decyl 8β-methyl-9α/β,15-dihydroxy-20-                          methyl-13-trans-prostenoates                              1127  decyl 8α-methyl-9-oxo-15-hydroxy-20-methyl-8-iso-13-trans-pros           tenoate (Example 1194)                                                                        decyl 8α-methyl-9α/β,15-dihydroxy-20                          -methyl-8-iso-13-trans-prostenoates                       1128  decyl 8β-methyl-9-oxo-15-hydroxy-20-methyl-13-cis-prostenoate             (Example 1194) decyl 8β-methyl-9α/β,15-dihydroxy-20-                          methyl-13-cis-prostenoates                                1229  ethyl 8α-methyl-9-oxo-15-hydroxy-20-methyl-8-iso-13-cis-proste           noate (Example 1194)                                                                          ethyl 8α-methyl-9α/β,15-dihydroxy-20                          -methyl-8-iso-13-cis-prostenoates                         1230  ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bis-homo-13-trans-proste           noate (Example 1195)                                                                          ethyl 8β-methyl-9α/β,15-dihydroxy-7a,                          7b-bis-homo-13-trans-prostenoates                         1231  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bis-homo-8-iso-13-trans           -prostenoate (Example 1195)                                                                   ethyl 8α-methyl-9α/β,15-dihydroxy-7a                          ,7b-bis-homo-8-iso-13-trans-prostenoates                  1232  ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bis-homo-13-cis-prosteno           ate (Example 1195)                                                                            ethyl 8β-methyl-9α/β,15-dihydroxy-7a,                          7b-bis-homo-13-cis-prostenoates                           1233  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bis-homo-8-iso-13-cis-p           rostenoate (Example 1195)                                                                     ethyl 8α-methyl-9α/β,15-dihydroxy-7a                          ,7b-bis-homo-8-iso-13-cis-prostenoates                    1234  ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bis-ethyl-13-trans-proste           noate (Example 1196)                                                                          ethyl 8β-methyl-9α/β,15-dihydroxy-2,2                          0-bis-ethyl-13-trans-prostenoates                         1235  ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-bis-ethyl-8-iso-13-trans           -prostenoate (Example 1196)                                                                   ethyl 8α-methyl-9α/β,15-dihydroxy-2,                          20-bis-ethyl-8-iso-13-trans-prostenoates                  1236  ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bis-ethyl-13-cis-prosteno           ate (Example 1196)                                                                            ethyl 8β-methyl-9α/β,15-dihydroxy-2,2                          0-bis-ethyl-13-cis-prostenoates                           1237  ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-bis-ethyl-8-iso-13-cis-p           rostenoate (Example 1196)                                                                     ethyl 8α-methyl-9α/β,15-dihydroxy-2,                          20-bis-ethyl-8-iso-13-cis-prostenoates                    1238  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-13-trans-           prostenoate (Example 1197)                                                                    ethyl 8β-methyl-9α/β,15-dihydroxy-3-o                          xa-16,16-dimethyl-13-trans-prostenoates                   1239  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-8-iso-13           -trans-prostenoate (Example 1197)                                                             ethyl 8α-methyl-9α/β,15-dihydroxy-3-                          oxa-16,16-dimethyl-8-iso-13-trans-prostenoates            1240  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-13-cis-pr           ostenoate (Example 1197)                                                                      ethyl 8β-methyl-9α/β,15-dihydroxy-3-o                          xa-16,16-dimethyl-13-cis-prostenoates                     1241  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-8-iso-13           -cis-prostenoate (Example 1197)                                                               ethyl 8α-methyl-9α/β,15-dihydroxy-3-                          oxa-16,16-dimethyl-8-iso-13-cis-prostenoates              1242  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-13-trans,17-cis-prostadi           enoate (Example 1198)                                                                         ethyl 8β-methyl-9α/β,15-dihydroxy-3-o                          xa-13-trans,17-cis-prostadienoates                        1243  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-trans,17-cis-p           rostadienoate (Example 1198)                                                                  ethyl 8α-methyl-9α/β,15-dihydroxy-3-                          oxa-8-iso-13-trans,17-cis-prostadienoates                 1224  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-13-cis,17-cis-prostadien           oate (Example 1198)                                                                           ethyl 8β-methyl-9α/β,15-dihydroxy-3-o                          xa-13-cis-17-cis-prostadienoates                          1245  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-cis,17-cis-pro           stadienoate (Example 1198)                                                                    ethyl 8α-methyl-9α/β,15-dihydroxy-3-                          oxa-8-iso-13-cis,17-cis-prostadienoates                   1246  ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-trans-prost           enoate (Example 1199)                                                                         ethyl 8β-methyl-9α/β,15-hydroxy-7-nor                          -20-methyl-13-trans-prostenoates                          1247  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-iso-13-tran           s-prostenoate (Example 1199)                                                                  ethyl 8α-methyl-9α/β,15-dihydroxy-7-                          nor-20-methyl-8-iso-13-trans-prostenoates                 1248  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-cis-proste           noate (Example 1199)                                                                          ethyl 8β-methyl-9α/β,15-dihydroxy-7-n                          or-20-methyl-13-cis-prostenoates                          1249  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-iso-13-cis-           prostenoate (Example 1199)                                                                    ethyl 8α-methyl-9α/β,15-dihydroxy-7-                          nor-20-methyl-8-iso-13-cis-prostenoates                   1250  ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-13-tra           ns-prostenoate (Example 1200)                                                                 ethyl 8β-methyl-9α/β,15-dihydroxy-2-f                          luoro-17,17-dimethyl-13-trans-prostenoates                1251  ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-8-iso           -13-trans-prostenoate (Example 1200)                                                          ethyl 8α-methyl-9α/β,15-dihydroxy-2-                          fluoro-17,17-dimethyl-8-iso-13-trans-prostenoates         1252  ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-13-cis           -prostenoate Example 1200)                                                                    ethyl 8β-methyl-9α/β,15-dihydroxy-2-f                          luoro-17,17-dimethyl-13-cis-prostenoates                  1253  ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-8-iso           -13-cis-prostenoate (Example 1200)                                                            ethyl 8α-methyl-9α/β,15-dihydroxy-2-                          fluoro-17,17-dimethyl-8-iso-13-cis-prostenoates           1254  ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-trans-prostenoate            (Example 1201) ethyl 8β-methyl-9α/β,15-dihydroxy-10a                          -homo-13-trans-prostenoates                               1255  ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-trans-prost           enoate (Example 1201)                                                                         ethyl 8α-methyl-9α/β,15-dihydroxy-10                          a-homo-8-iso-13-trans-prostenoates                        1256  ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-cis-prostenoate              (Example 1201) ethyl 8β-methyl-9α/β,15-dihydroxy-10a                          -homo-13-cis-prostenoates                                 1257  ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-cis-prosten           oate (Example 1201)                                                                           ethyl 8α-methyl-9α/β,15-dihydroxy-10                          a-homo-8-iso-13-cis-prostenoates                          1258  ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13-trans-pr           ostenoate (Example 1202)                                                                      ethyl 8β-methyl-9α/β,15-dihydroxy-2-p                          henyl-20-methyl-13-trans-prostenoates                     1259  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8-iso-13-t           rans-prostenoate (Example 1202)                                                               ethyl 8α-methyl-9α/β,15-dihydroxy-2-                          phenyl-20-methyl-8-iso-13-trans-prostenoates              1260  ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13-cis-pros           tenoate (Example 1202)                                                                        ethyl 8β-methyl-9α/β,15-dihydroxy-2-p                          henyl-20-methyl-13-cis-prostenoates                       1261  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8-iso-13-c           is-prostenoates (Example 1202)                                                                ethyl 8α-methyl-9α/β,15-dihydroxy-2-                          phenyl-20-methyl-8-iso-13-cis-prostenoates                1262  methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostat           rienoate (Example 1203)                                                                       methyl 8β-methyl-9α/β,15-dihydroxy-5-                          cis,13-trans,17-cis-prostatrienoates                      1263  methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans,17-cis-           prostatrienoate (Example 1203)                                                                methyl 8α-methyl-9α/β,15-dihydroxy-8                          -iso-5-cis,13-trans,17-cis-prostatrienoates               1264  methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis,17-cis-prostatri           enoate (Example 1203)                                                                         methyl 8β-methyl-9α/β,15-dihydroxy-5-                          cis,13-cis,17-cis-prostatrienoates                        1265  methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis,17-cis-pr           ostatrienoate (Example 1203)                                                                  methyl 8α-methyl-9α/β,15-dihydroxy-8                          -iso-5-cis,13-cis,17-cis-prostatrienoates                 1266  ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans-prostadienoate            (Example 1204) ethyl 8β-methyl-9α/β,15-dihydroxy-5-c                          is,13-trans-prostadienoates                               1267  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans-prostadi           enoate (Example 1204)                                                                         ethyl 8α-methyl-9α/β,15-dihydroxy-8-                          iso-5-cis,13-trans-prostadienoates                        1268  ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis-prostadienoate              (Example 1204) ethyl 8β-methyl-9α/β,15-dihydroxy-5-c                          is,13-cis-prostadienoates                                 1269  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis-prostadien           oate (Example 1204)                                                                           ethyl 8α-methyl-9α/β,15-dihydroxy-8-                          iso-5-cis,13-cis-prostadienoates                          1270  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-trans-prosta           dienoate (Example 1205)                                                                       ethyl 8β-methyl-9α/β,15-dihydroxy-20-                          ethyl-5-cis,13-trans-prostadienoates                      1271  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis,13-trans           -prostadienoate (Example 1205)                                                                ethyl 8α-methyl-9α/β,15-dihydroxy-20                          -ethyl-8-iso-5-cis,13-trans-prostadienoates               1272  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-cis-prostadi           enoate (Example 1205)                                                                         ethyl 8β-methyl-9α/β,15-dihydroxy-20-                          ethyl-5-cis,13-cis-prostadienoates                        1273  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis,13-cis-p           rostadienoate (Example 1205)                                                                  ethyl 8α-methyl-9α/β,15-dihydroxy-20                          -ethyl-8-iso-5-cis,13-cis-prostadienoates                 ______________________________________                                    

EXAMPLES 1274- 1299

In the manner of Example 93, the various cyclopentenones of Table 36, which follows, are converted to the corresponding 4-bromo derivatives.

                  TABLE 36                                                         ______________________________________                                               Starting                                                                 Ex-   Cyclopentenone Product 4-Bromocyclo-                                     ample of Example     pentenones                                                ______________________________________                                         1274  13             4-bromo-2-(6-carbethoxyhexyl)-cyclopent-2-en-1-one        1275  83             4-bromo-2-(6-carbomethoxyhexyl)cyclopent-2-en-1-one       1276  15             4-bromo-2-(4-carbethoxybutyl)cyclopent-2-en-1-one         1277  14             4-bromo-2-(3-carbethoxypropyl)-cyclopent-2-en-1-one       1278  2              4-bromo-2-(4-carboxybutyl)cyclopent-2-en-1-one            1279  5              4-bromo-2-(3-carboxypropyl)cyclopent-2-en-1-one           1280  22             4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one            1281  23             4-bromo-2-(8-carboethoxyoctyl)cyclopent-2-en-1-one        1282  30             4-bromo-2-(6-carboxyoctyl)cyclopent-2-en-1-one            1283  31             4-bromo-2-(6-carbethoxyoctyl)cyclopent-2-en-1-one         1284  92             4-bromo-2-(6-carboxy-5,5-dimethylhexyl)cyclopent-2-en                          -1-one                                                    1285  41             4-bromo-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-2                          -en-1-one                                                 1286  45             4-bromo-2-(6-carboxy-5-oxahexyl)cyclopent-2-en-1-one                           3                                                         1287  46             4-bromo-2-(6-carbethoxy-5-oxahexyl)cyclopent-2-en-1-o                          ne                                                        1288  69             4-bromo-2-(6-carboxy-6-fluorohexyl)cyclopent-2-en-1-o                          ne                                                        1289  70             4-bromo-2-(6-carbethoxy-6-fluorohexyl)cyclopent-2-en-                          1-one                                                     1290  52             4-bromo-2-(5-carboxypentyl)cyclopent-2-en-1-one           1291  53             4-bromo-2-(5-carbethoxypentyl)cyclopent-2-en-1-one        1292  73             4-bromo-2-(7-carboxyheptyl)cyclopent-2-en-1-one           1293  74             4-bromo-2-(7-carbethoxyheptyl)cyclopent-2-en-1-one        1294  78             4-bromo-2-(6-carboxy-6-phenylhexyl)cyclopent-2-en-1-o                          ne                                                        1295  79             4-bromo-2-(6-carbethoxy-6-phenylhexyl)cyclopent-2-en-                          1-one                                                     1296  81             4-bromo-2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one                          b                                                         1297  82             4-bromo-2-(6-carbo-isopropoxyhexyl)cyclopent-2-en-1-o                          ne                                                        1298  84             4-bromo-2-(6-carbo-n-decyloxyhexyl)cyclopent-2-en-1-o                          ne                                                        1299  98             4-bromo-2-(6-carboxyheptyl)-cyclopent-2-en-1-one          ______________________________________                                    

EXAMPLE 1300 Preparation of 4-hydroxy-2-(8-carboxyoctyl)cyclopent-2-en-1-one

To a stirred solution of 57.2 g. of crude 4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 1280) in 500 ml. of acetone and 325 ml. of water at 3°C. is added 44.1 g. (0.226 moles) of silver fluoborate during a 15 minute period. The mixture is stirred at 0°-3°C. for 2 hours and filtered. The filtrate is diluted with water, saturated with solid sodium chloride, and extracted with ether. The extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Partition chromatography of the residue on Celite gives white crystals, m.p. 58°-66°C., λ_(max).^(MeOH) = 223 mμ (7800); ν max (KBr) = 3340 (hydroxyl groups), 1705 (carbonyl groups), and 1625 cm⁻ ¹ (olefin group).

EXAMPLE 1301 Preparation of 4-acetoxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

A mixture of 51.6 g. (0.137 moles) of crude 4-bromo-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g. (0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid is stirred at reflux for 4.5 hours. The mixture is cooled, and solids are removed by filtration. The filtrate is concentrated and extracted with hot hexane. The extract is washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over mangesium sulfate, and concentrated to give an oil. The crude product is distilled at reduced pressure to give a liquid, b.p. 152°-163°C. (0.01 mm); λ_(max).^(MeOH) = 223 mμ (10700); νmax. = 1745 (ester carbonyl groups), 1725 (ketone carbonyl groups), and 1235 cm⁻ ¹ (acetoxy group).

Examples 1302-1326

By the procedure of Example 94 the various 4-bromocyclopentenones of the following Table 37 are solvolyzed in acetone-water in the presence of silver fluoborate to provide the product 4-hydroxycyclopentenones of the Table.

                  Table 37                                                         ______________________________________                                               Starting 4-bromo                                                                              Product                                                   Ex-   cyclopentenones                                                                               4-Hydroxycyclopent-2-                                     ample of Example                                                               en-1-ones                                                                      ______________________________________                                         1302  1274           4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one       1303  1275           4-hydroxy-2-(6-carbomethoxyhexyl)cyclopent-2-en-1-one                          N                                                         1304  1276           4-hydroxy-2-(4-carbethoxybutyl)cyclopent-2-en-1-one       1305  1277           4-hydroxy-2-(3-carbethoxypropyl)cyclopent-2-en-1-one                           O                                                         1306  1278           4-hydroxy-2-(4-carboxybutyl)cyclopent-2-en-1-one          1307  1279           4-hydroxy-2-(3-carboxypropyl)cyclopent-2-en-1-one         1308  1281           4-hydroxy-2-(8-carbethoxyoctyl)cyclopent-2-en-1-one       1309  1282           4-hydroxy-2-(6-carboxyoctyl)cyclopent-2-en-1-one          1310  1283           4-hydroxy-2-(6-carbethoxyoctyl)cyclopent-2-en-1-one       1311  1284           4-hydroxy-2-(6-carboxy-5,5-dimethylhexyl)-cyclopent-2                          -en-1-one                                                 1312  1285           4-hydroxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent                          -2-en-1-one                                               1313  1286           4-hydroxy-2-(6-carboxy-5-oxahexyl)cyclopent-2-en-1-on                          e                                                         1314  1287           4-hydroxy-2-(6-carbethoxy-5-oxahexyl)-cyclopent-2-en-                          1-one                                                     1315  1288           4-hydroxy-2-(6-carboxy-6-fluorohexyl)cyclopent-2-en-1                          -one                                                      1316  1289           4-hydroxy-2-(6-carbethoxy-6-fluorohexyl)cyclopent-2-e                          n-1-one                                                   1317  1290           4-hydroxy-2-(5-carboxypentyl)cyclopent-2-en-1-one         1318  1291           4-hydroxy-2-(5-carbethoxypentyl)cyclopent-2-en-1-one                           A                                                         1319  1292           4-hydroxy-2-(7-carboxyheptyl)cyclopent-2-en-1-one         1320  1293           4-hydroxy-2-(7-carbethoxyheptyl)cyclopent-2-en-1-one                           M                                                         1321  1294           4-hydroxy-2-(6-carboxy-6-phenylhexyl)cyclopent-2-en-1                          -one                                                      1322  1295           4-hydroxy-2-(6-carbethoxy-6-phenylhexyl)cyclopent-2-e                          n-1-one                                                   1323  1296           4-hydroxy-2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-o                          ne                                                        1324  1297           4-hydroxy-2-(6-carboisopropoxyhexyl)cyclopent-2-en-1-                          one                                                       1325  1298           4-hydroxy-2-(6-carbo-n-decyloxyhexyl)cyclopent-2-en-1                          -one                                                      1326  1299           4-hydroxy-2-(6-carboxyheptyl)cyclopent-2-en-1-one         ______________________________________                                    

Examples 1327-1337

By the procedure of Example 95, the various 4-hydroxycyclopentenones of Table 38, which follows, are converted to the tetrahydropyranyl 4-tetrahydropyranyloxycyclopentenone esters of the table.

                  Table 38                                                         ______________________________________                                               Starting 4-hy- Product Tetrahydropyran-                                  Ex-   droxycyclopenten-                                                        2'-yl 4-tetrahydropy-                                                          ample one of Example ran-2'-yl-oxycyclopent-                                   2-en-1-ones                                                                    ______________________________________                                         1327  1306           4-tetrahydropyran-2'-yloxy-2-(4-carbotetrahydropyran-                          2'-yloxybutyl)cyclopent-2-en-1-one                        1328  1307           4-tetrahydropyran-2'-yloxy-2-(3-carbotetrahydropyran-                          2'-yloxypropyl)cyclopent-2-en-1-one                       1329  1300           4-tetrahydropyran-2'-yloxy-2-(8-carbotetrahydropyran-                          2'-yloxyoctyl)cyclopent-2-en-1-one                        1330  1309           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxyoctyl)cyclopent-2-en-1-one                        1331  1311           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxy-5,5-dimethylhexyl)cyclopent-2-en-1-one           1332  1313           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxy-5-oxahexyl)cyclopent-2-en-1-one                  1333  1315           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxy-6-fluorohexyl)cyclopent-2-en-1-one               1334  1317           4-tetrahydropyran-2'-yloxy-2-(5-carbotetrahydropyran-                          2'-yloxypentyl)cyclopent-2-en-1-one                       1335  1319           4-tetrahydropyran-2'-yloxy-2-(7-carbotetrahydropyran-                          2'-yloxyheptyl)cyclopent-2-en-1-one                       1336  1321           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxy-6-phenylhexyl)cyclopent-2-en-1-one               1337  1326           4-tetrahydropyran-2'-yloxy-2-(6-carbotetrahydropyran-                          2'-yloxyheptyl)cyclopent-2-en-1-one                       ______________________________________                                    

EXAMPLE 1338 Preparation of 4-tetrahydropyranyloxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 674 mg. (2.64 mmoles) of 4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1302) and 2.22 g. (26.4 mmoles) of dihydropyran in 2.6 ml. of methylene chloride is added 5.0 mg. (0.026 mmoles) of p-toluenesulfonic acid monohydrate. After stirring for 20 minutes at room temperature the solution is diluted with ether and poured into saturated sodium chloride solution containing a little sodium bicarbonate. The organic phase is separated and washed with saturated sodium chloride solution. The extract is dried over magnesium sulfate, and volatile matter is evaporated at reduced pressure to give an oil, λ_(max).^(MeOH) = 224 mμ (7950); max. = 1735 (ester carbonyl group), 1710 (ketone carbonyl group), and 1030 cm.sup.⁻¹ (tetrahydropyranyloxy group).

EXAMPLE 1339-1352

In the manner of Example 1338 the alkyl 4-hydroxycyclopentenone esters of Table 39, which follows, are converted to the corresponding 4-tetrahydropyranyloxy alkyl esters of the table.

                  TABLE 39                                                         ______________________________________                                               Starting 4-                                                                    hydroxycyclo-  4-tetrahydropyran-                                        Ex-   pentenone Esters                                                                              2'yloxycyclopent-                                         ample of Example     2-en-1-one esters                                         ______________________________________                                         1339  1303           4-tetrahydropyran-2'yloxy-2-(6-carbomethoxyhexyl)cycl                          opent-2-en-1-one -1340 1304 4-tetrahydropyran-2'yloxy                          -2-(4-carbethoxybutyl)cyclopent-2-en-1-one                1341  1305           4-tetrahydropyran-2'yloxy-2-(3-carbethoxypropyl)cyclo                          pent-2-en-1-one                                           1342  1308           4-tetrahydropyran-2'yloxy-2-(8-carbethoxyoctyl)cyclop                          ent-2-en-1-one                                            1343  1310           4-tetrahydropyran-2'yloxy-2-(6-carbethoxyoctyl)cyclop                          ent-2-en-1-one                                            1344  1312           4-tetrahydropyran-2'yloxy-2-(6-carbethoxy-5,5-dimethy                          lhexyl)cyclopent-2-en-1-one                               1345  1314           4-tetrahydropyran-2'yloxy-2-(6-carbethoxy-5-oxahexyl)                          cyclopent-2-en-1-one                                      1346  1316           4-tetrahydropyran-2'yloxy-2-(6-carbethoxy-6-fluorohex                          yl)cyclopent-2-en-1-one                                   1347  1318           4-tetrahydropyran-2'yloxy-2-(5-carbethoxypentyl)cyclo                          pent-2-en-1-one                                           1348  1320           4-tetrahydropyran-2'yloxy-2-(7-carbethoxyheptyl)cyclo                          pent-2-en-1-one                                           1349  1322           4-tetrahydropyran-2'yloxy-2-(6-carbethoxy-6-phenylhex                          yl)cyclopent-2-en-1-one                                   1350  1323           4-tetrahydropyran-2'yloxy-2-(6-carbo-n-butoxyhexyl)cy                          clopent-2-en-1-one                                        1351  1324           4-tetrahydropyran-2'yloxy-2-(6-carbo-isopropoxyhexyl)                          cyclopent-2-en-1-one                                      1352  1325           4-tetrahydropyran-2'yloxy-2-(6-carbo-n-decyloxyhexyl)                          cyclopent-2-en-1-one                                      ______________________________________                                    

EXAMPLE 1353 Preparation of 8β-methyl-prostaglandin E₁, 8α-methyl-8-iso-prostaglandin E₁, 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid, and 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic acid

The Grignard reagent, prepared as described in Example 1187 from 1.54 g. of magnesium, 22.5 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 30 ml. of tetrahydrofuran, is added to an ice cooled solution of 17.75 g. of 11-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxyhexyl)-2-cyclopentenone (Example 95) and 1.25 g. of copper (I) iodide-tri-n-butylphosphine complex in 30 ml. of tetrahydrofuran over 15 minutes under an inert atmosphere. The mixture is stirred with cooling for 0.5 hour. To the mixture is then added 100 g. of methyl iodide, the cooling bath is then removed and the mixture is stirred at ambient temperatures for 48 hours. The mixture is then poured into ice cold saturated ammonium chloride solution and the layers are separated. The aqueous phase is washed with ether and combined organic phase and washings are washed with saturated brine, and evaporated in vacuo. The residue is heated to 45°C. for 5 hours with 840 ml. of 4:2:1 tetrahydrofuranacetic acid-water under an inert atmosphere and is then evaporated to dryness in vacuo. The residue is chromatographed upon Silic AR CC-4 using a benzene-ethyl acetate gradient as eluent to yield the title compounds as a mixture of 8β-methyl-prostaglandin E₁ and 8α-methyl-8-iso-prostaglandin E₁ and a mixture of 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid and 8α-methyl-9-oxo-11α,15-dihydroxy 8-isocis-8α isomers; resolution of the mixtures is then accomplished by a combination of partition chromatography and thin-layer chromatography.

EXAMPLES 1354-1386

Treatment of the blocked 4-oxycyclopent-2-en-1-ones listed in Table 40 below by the procedure described in Example 1353 with the Grignard reagents, prepared by the procedure described in Example 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyl iodide furnishes the product 8α- and 8β-methyl prostenoates of the table. The products of Examples 1354-1378 inclusive are initially obtained as the corresponding 15-O-triphenylmethyl-11-O-tetrahydropyranyl tetrahydropyranyl esters. These blocking groups are then cleaved by the procedure described in Example 1353 by treatment at 45°C. for 5 hours with 4:2:1 tetrahydrofuran:acetic acid:water. The alkyl esters products of Examples 1379-1385 inclusive are obtained initially as the corresponding 15-O-triphenylmethyl-11-O-tetrahydropyranyl derivatives. These 11- and 15-hydroxy blocking groups are then cleaved by the deblocking procedure described in Example 1353. The products of Example 1386 are initially obtained as the corresponding 15-O-triphenylmethyl derivatives, which are cleaved hydrolytically to the listed free 15-ols by the process described in Example 1353.

                                      TABLE 40                                     __________________________________________________________________________     Ex- Starting blocked                                                                          Starting 1-bromo-                                               ample                                                                              4-oxycyclopent-                                                                           3-triphenylmethoxy-                                                 2-en-1-one of                                                                             1-trans-alkene of                                                   Example    Example    Product 8-methylprostenoic acid                      __________________________________________________________________________     1354                                                                               95         1175       8β-methyl-9-oxo-11α,15-dihydroxy-16,1                               6-oimethyl-13-trans-prostenoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-16,                               16-dimethyl-8-iso-13-trans-prostenoic acid                                     8β-methyl-9-oxo-11α,15-dihydroxy-16,1                               6-dimethyl-13-cis-prostenoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-16,                               16-dimethyl-8-iso-13-cis-prostenoic acid             1355                                                                               95         1178       8β-methyl-9-oxo-11α,15-dihydroxy,17,1                               7-dimethyl-13-trans-prostenoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-17,                               17-dimethyl-8-iso-13-trans-prostenoic acid                                     8β-methyl-9-oxo-11α,15-dihydroxy-17,1                               7-dimethyl-13-cis-prostenoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-17,                               17-dimethyl-8-iso-13-cis-prostenoic acid             1356                                                                               95         1182       8β-methyl-9-oxo-11α,15-dihydroxy-13-t                               rans,17-cis-prostadienoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-13-trans,17-cis-prostadienoic acid                                          8β-methyl-9-oxo-11α,15-dihydroxy-13-c                               is,17-cis-prostadienoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-13-cis,17-cis-prostadienoic acid                  1357                                                                               95         1185       8β-methyl-9-oxo-11α,15-dihydroxy-20-e                               thyl-13-trans-prostenoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-20-                               ethyl-8-iso-13-trans-prostenoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-20-e                               thyl-13-cis-prostenoic acid                                                    8α-methyl-9-oxo-11α,15-dihydroxy-20-                               ethyl-8-iso-13-cis-prostenoic acid                   1358                                                                               1327       728        8β-methyl-9-oxo-11α,15-dihydroxy-6,7-                               dinor-13-trans-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-6,7                               -dinor-8-iso-13-trans-prostenoic acid                                          8β-methyl-9-oxo-11α,15-dihydroxy-6,7-                               dinor-13-cis-prostenoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-6,7                               -dinor-8-iso-13-cis-prostenoic acid                  1359                                                                               1328       1186       8β-methyl-9-oxo-11α,15-dihydroxy-5,6,                               7-trinor-20-methyl-13-trans-prostenoic acid                                    8α-methyl-9-oxo-11α,15-dihydroxy-5,6                               ,7-trinor-20-methyl-8-iso-13-trans-prostenoic                                  acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-5,6,                               7-trinor-20-methyl-13-cis-prostenoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-5,6                               ,7-trinor-20-methyl-8-iso-13-cis-prostenoic                                    acid                                                 1360                                                                               1329       728        8β-methyl-9-oxo-11α,15-dihydroxy-7a,7                               b-bishomo-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-7a,                               7b-bishomo-8-iso-13-trans-prostenoic acid                                      8β-methyl-9-oxo-11α,15-dihydroxy-7a,7                               b-bishomo-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-7a,                               7b-bishomo-8-iso-13-cis-prostenoic acid              1361                                                                               1330       728        8β-methyl-9-oxo-11α,15-dihydroxy-2-et                               hyl-13-trans-prostenoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-2-e                               thyl-8-iso-13-trans-prostenoic acid                                            8β-methyl-9-oxo-11α,15-dihydroxy-2-et                               hyl-13-cis-prostenoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-2-e                               thyl-8-iso-13-cis-prostenoic acid                    1362                                                                               1331       1186       8β-methyl-9-oxo-11α,15-dihydroxy-3,3,                               20-trimethyl-13-trans-prostenoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-3,3                               ,20-trimethyl-8-iso-13-trans-prostenoic acid                                   8β-methyl-9-oxo-11α,15-dihydroxy-3,3,                               20-trimethyl-13-cis-prostenoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-3,3                               ,20-trimethyl-8-iso-13-cis-prostenoic acid           1363                                                                               1332       728        8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-13-trans-prostenoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-8-iso-13-trans-prostenoic acid                                              8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-13-cis-prostenoic acid                                                       8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-8-iso-13-cis-prostenoic acid                      1364                                                                               1332       1175       8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-16,16-dimethyl-13-trans-prostenoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-16,16-dimethyl-8-iso-13-trans-prostenoic                                    acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-16,16-dimethyl-13-cis-prostenoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-16,16-dimethyl-8-iso-13-cis-prostenoic acid       1365                                                                               1332       1182       8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-13-trans,17-cis-prostadienoic acid                                           8α-methyl -9-oxo-11α,15-dihydroxy-3-                               oxa-8-iso-13-trans,17-cis-prostadienoic acid                                   8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-13-cis,17-cis-prostadienoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-8-iso-13-cis,17-cis-prostadienoic acid            1366                                                                               1332       1185       8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-20-ethyl-13-trans-prostenoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-20-ethyl-8-iso-13-trans-prostenoic acid                                     8β-methyl-9-oxo-11α,15-dihydroxy-3-ox                               a-20-ethyl-13-cis-prostenoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-3-o                               xa-20-ethyl-8-iso-13-cis-prostenoic acid             1367                                                                               1333       1178       8β-methyl-9-oxo-11α,15-dihydroxy-2-fl                               uoro-17,17-dimethyl-13-trans-prostenoic acid                                   8α-methyl-9-oxo-11α,15-dihydroxy-2-f                               luoro-17,17-dimethyl-8-iso-13-trans-prostenoic                                 acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-2-fl                               uoro-17,17-dimethyl-13-cis-prostenoic acid                                     8α-methyl-9-oxo-11α,15-dihydroxy-2-f                               luoro-17,17-dimethyl-8-iso-13-cis-prostenoic                                   acid                                                 1368                                                                               1334       728        8β-methyl-9-oxo-11α,15-dihydroxy-7-no                               r-13-trans-prostenoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-7-n                               or-8-iso-13-trans-prostenoic acid                                              8β-methyl-9-oxo-11α,15-dihydroxy-7-no                               r-13-cis-prostenoic acid                                                       8α-methyl-9-oxo-11α,15-dihydroxy-7-n                               or-8-iso-13-cis-prostenoic acid                      1369                                                                               1335       1175       8β-methyl-9-oxo-11α,15-dihydroxy-7a-h                               omo-16,16-dimethyl-13-trans-prostenoic acid                                    8α-methyl-9-oxo-11α,15-dihydroxy-7a-                               homo-16,16-dimethyl-8-iso-13-trans-prostenoic                                  acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-7a-h                               omo-16,16-dimethyl-13-cis-prostenoic acid                                      8α-methyl-9-oxo-11α                                                ,15-dihydroxy-7a-homo-16,16-dimethyl-8-iso-13-ci                               s-prostenoic acid                                    1370                                                                               1336       728        8β-methyl-9-oxo-11α,15-dihydroxy-2-ph                               enyl-13-trans-prostenoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-2-p                               henyl-8-iso-13-trans-prostenoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-2-ph                               enyl-13-cis-prostenoic acid                                                    8α-methyl-9-oxo-11α,15-dihydroxy-2-p                               henyl-8-iso-13-cis-prostenoic acid                   1371                                                                               1337       1182       8β-methyl-9-oxo-11α,15-dihydroxy-2-me                               thyl-13-trans,17-cis-prostadienoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-2-m                               ethyl-8-iso-13-trans,17-cis-prostadienoic acid                                 8β-methyl-9-oxo-11α,15-dihydroxy-2-me                               thyl-13-cis,17-cis-prostadienoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-2-m                               ethyl-8-iso-13-cis,17-cis-prostadienoic acid         1372                                                                               1121       728        8β-methyl-9-oxo-11α,15-dihydroxy-5-ci                               s,13-trans-prostadienoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-5-cis,13-trans-prostadienoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-5-ci                               s,13-cis-prostadienoic acid                                                    8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-5-cis,13-cis-prostadienoic acid                   1373                                                                               1121       1182       8β-methyl-9-oxo-11α,15-dihydroxy-5-ci                               s,13-trans,17-cis-prostatrienoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-5-cis,13-trans,17-cis-prostatrienoic acid                                   8β-methyl-9-oxo-11α,15-dihydroxy-5-ci                               s,13-cis,17-cis-prostatrienoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-8-i                               so-5-cis,13-cis,17-cis-prostatrienoic acid           1374                                                                               1121       1175       8β-methyl-9-oxo-11α,15-dihydroxy-16,1                               6-dimethyl-5-cis,13-trans,prostadienoic acid                                   8α-methyl-9-oxo-11α,15-dihydroxy-16,                               16-dimethyl-8-iso-5-cis,13-trans-prostadienoic                                 acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-16,1                               6-dimethyl-5-cis,13-cis-prostadienoic acid                                     8α-methyl-9-oxo-11α,15-dihydroxy-16,                               16-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                   acid                                                 1375                                                                               1122       1186       8β-methyl-9-oxo-11α,15-dihydroxy-4-no                               r-20-methyl-5-cis,13-trans-prostadienoic acid                                  8α-methyl-9-oxo-11α,15-dihydroxy-4-n                               or-20-methyl-8-iso-5-cis,13-trans-prostadienoic                                acid                                                                           8β-methyl-9-oxo-11α,15-dihydroxy-4-no                               r-20-methyl-5-cis,13-cis-prostadienoic acid                                    8β-methyl-9-oxo-11α,15-dihydroxy-4-no                               r-20-methyl-8-iso-5-cis,13-cis-prostadienoic                                   acid                                                 1376                                                                               1123       1178       8β-methyl-9-oxo-11α,15-dihydroxy-4a-h                               omo-17,17-dimethyl-5-cis,13-trans-prostadienoic                                acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a-                               homo-17,17-dimethyl-8-iso-5-cis,13-cis-prostadie                               noic acid                                                                      8β-methyl-9-oxo-11α,15-dihydroxy-4a-h                               omo-17,17-dimethyl-5-cis,13-cis-prostadienoic                                  acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a-                               homo-17,17-dimethyl-8-iso-5-cis,13-cis-prostadie                               noic acid                                            1377                                                                               1124       1185       8β-methyl-9-oxo-11α,15-dihydroxy-4a,4                               b-bishomo-20-ethyl-5-cis,13-trans-prostadienoic                                acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a,                               4b-bishomo-20-ethyl-8-iso-5-cis,13-trans-prostad                               ienoic acid                                                                    8β-methyl-9-oxo-11α,15-dihydroxy-4a,4                               b-bishomo-20-ethyl-5-cis,13-cis-prostadienoic                                  acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a,                               4b-bishomo-20-ethyl-8-iso-5-cis,13-cis-prostadie                               noic acid                                            1378                                                                               1124       1182       8β-methyl-9-oxo-11α,15-dihydroxy-4a,4                               b-bishomo-5-cis,13-trans,17-cis-prostatrienoic                                 acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a,                               4b-bishomo-8-iso-5-cis,13-trans,17-cis-prostatri                               enoic acid                                                                     8β-methyl-9-oxo-11α,15-dihydroxy-4a,4                               b-bishomo-5-cis,13-cis,17-cis-prostatrienoic                                   acid                                                                           8α-methyl-9-oxo-11α,15-dihydroxy-4a,                               4b-bishomo-8-iso-5-cis,13-cis-17-cis-prostatrien                               oic acid                                             1379                                                                               1339       1186       Methyl 8β-methyl-9-oxo-11α,15-dihydro                               xy-20-methyl-13-trans-prostenoate                                              Methyl 8α-methyl-9-oxo-11α,15-dihydr                               oxy-20-methyl-8-iso-13-trans-prostenoate                                       Methyl 8β-9-oxo-11α,15-dihydroxy-20-m                               ethyl-13-cis-prostenoate                                                       Methyl 8α-methyl-9-oxo-11α,15-dihydr                               oxy-20-methyl-8-iso-13-cis-prostenoate               1380                                                                               1342       1182       Ethyl 8β-methyl-9-oxo-11α                                           ,15-dihydroxy-7a,7b-bishomo-13-trans,17-cis-pros                               tadienoate                                                                     Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-7a,7b-bishomo-8-iso-13-trans,17-cis-prostadie                               noate                                                                          Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-7a,7b-bishomo-13-cis,17-cis-prostadienoate                                   Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-7a,7b-bishomo-8-iso-13-cis,17-cis-prostadieno                               ate                                                  1381                                                                               1343       1175       Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-2-ethyl-16,16-dimethyl-13-trans-prostenoate                                  Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-2-ethyl-16-16-dimethyl-8-iso-13-trans-prosten                               oate                                                                           Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-2-ethyl-16,16-dimethyl-13-cis-prostenoate                                    Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-2-ethyl-16,16-dimethyl-8-iso-13-cis-prostenoa                               te                                                   1382                                                                               1344       1178       Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-3,3-17,17-tetramethyl-13-trans-prostenoate                                   Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-3,3-17,17-tetramethyl-8-iso-13-trans-prosteno                               ate                                                                            Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-3,3-17,17-tetramethyl-13-cis-prostenoate                                     Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-3,3-17,17-tetramethyl-8-iso-13-cis-prostenoat                               e                                                    1383                                                                               1345       1178       Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-3-oxa-17,17-dimethyl-13-trans-prostenoate                                    Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-3-oxa-17,17-dimethyl-8-iso-13-trans-prostenoa                               te                                                                             Ethyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-3-oxa-17,17-dimethyl-13-cis-prostenoate                                      Ethyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-3-oxa-17,17-dimethyl-8-iso-13-cis-prostenoate                               .                                                    1384                                                                               1350       728        Butyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-13-trans-prostenoate                                                         Butyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-8-iso-13-trans-prostenoate                                                  Butyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-13-cis-prostenoate                                                           Butyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-8-iso-13-cis-prostenoate                          1385                                                                               1352       1182       Decyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-13-trans,17-cis-prostadienoate                                               Decyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-8-iso-13-trans,17-cis-prostadienoate                                        Decyl 8β-methyl-9-oxo-11α,15-dihydrox                               y-13-cis-17-cis-prostadienoate                                                 Decyl 8α-methyl-9-oxo-11α,15-dihydro                               xy-8-iso-13-cis,17-cis-prostadienoate                1386                                                                               1301       728        Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-                               hydroxy-13-trans-prostenoate                                                   Ethyl 8α-methyl-9-oxo-11α-acetoxy-15                               -hydroxy-8-iso-13-trans-prostenoate                                            Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-                               hydroxy-13-cis-prostenoate                                                     Ethyl 8α-methyl-9-oxo-11α-acetoxy-15                               -hydroxy-8-iso-13-cis-prostenoate                    __________________________________________________________________________

EXAMPLE 1387 Preparation of 8β-methyl-prostaglandin A₁

A mixture of 0.30 g. of 8β-methyl-prostaglandin E₁ (Example 1353) and 10 ml. of 1:9 aqueous acetic acid is heated to 65°C. for 18 hours under an inert atmosphere. The solvent is removed in vacuo and the residue is purified upon Silic AR-CC-4 using a benzene-ethylacetate gradient to yield the title compound.

EXAMPLES 1388-1522

Treatment of the designated 8-methyl-9-oxo-11-hydroxy-prostenoic acid derivatives of Table 41 below with 1:9 aqueous acid and purification all as described in Example 1387 gives the corresponding 8-methyl-9-oxo-10,13-prostadienoic acids and esters of the table.

                  TABLE 41                                                         ______________________________________                                               Starting 9-oxo-                                                                               Product 8-methyl-9-oxo-                                   Exam- 11-hydroxy                                                               10,13-prostadienoic                                                            ple   derivative     acids or esters                                           ______________________________________                                         1388  8α-methyl-8-iso-prostaglandin E.sub.1 (Example                                          8α-methyl-8-iso-prostaglandin A.sub.1               1389  8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid             (Example 1353) 8β-methyl-11α,15-dihydroxy-10,13-cis-prost                          adienoic acid                                             1390  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic            acid (Example 1353)                                                                          8α-methyl-11α,15-dihydroxy-8-iso-10,13-ci                          s-prostadienoic acid                                      1391  8β-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-13-trans-           prostenoic acid (Example 1354)                                                                8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl                                 10,13-trans-prostadienoic acid                            1392  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-13           -trans-prostenoic acid (Example 1354)                                                         8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -10,13-trans-prostadienoic acid                           1393  8β-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-13-cis-pr           ostenoic acid (Example 1354)                                                                  8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl                                 10,13-cis-prostadienoic acid                              1394  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-13           -cis-prostenoic acid (Example 1354)                                                           8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -10,13-cis-prostadienoic acid                             1395  8β-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl                     13-trans-prostenoic acid (Example 1355)                                                       8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl                                 10,13-trans-prostadienoic acid                            1396  8α-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl-8-iso-13           -trans-prostenoic acid (Example 1355)                                                         8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso                          -10,13-trans-prostadienoic acid                           1397  8β-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl                     13-cis-prostenoic acid (Example 1355)                                                         8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl                                 10,13-cis-prostadienoic acid                              1398  8α-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl-8-iso-13           -cis-prostenoic acid (Example 1355)                                                           8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso                          -10,13-cis-prostadienoic acid                             1399  8β-methyl-9-oxo-11α,15-dihydroxy-13-trans,17-cis-prostadi           enoic acid (Example 1356)                                                                     8β-methyl-9-oxo-15-hydroxy-10,13-trans,17-cis-pr                          ostatrienoic acid                                         1400  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-trans,17-cis-p           rostadienoic acid (Example 1356)                                                              8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-trans,-1                          7-cis-prostatrienoic acid                                 1401  8β-methyl-9-oxo-11α,15-dihydroxy-13-cis,17-cis-prostadien           oic acid (Example 1356)                                                                       8β-methyl-9-oxo-15-hydroxy-10,13-cis,17-cis-pros                          tatrienoic acid                                           1402  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis,-17-cis-pr           ostadienoic acid (Example 1356)                                                               8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-cis,-17-                          cis-prostatrienoic acid                                   1403  8β-methyl-9-oxo-11α,15-dihydroxy-20-ethyl-13-trans-proste           noic acid (Example 1357)                                                                      8β-methyl-9-oxo-15-hydroxy-20-ethyl-10,13-trans-                          prostadienoic acid                                        1404  8α-methyl-9-oxo-11α,15-dihydroxy-20-ethyl-8-iso-13-trans           -prostenoic acid (Example 1357)                                                               8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-10,13                          -trans-prostadienoic acid                                 1405  8β-methyl-9-oxo-11α,15-dihydroxy-20-ethyl-13-cis-prosteno           ic acid (Example 1357)                                                                        8β-methyl-9-oxo-15-hydroxy-20-ethyl-10,13-cis-pr                          ostadienoic acid                                          1406  8α-methyl-9-oxo-11α,15-dihydroxy-20-ethyl-8-iso-13-cis-p           rostenoic acid (Example 1357)                                                                 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-10,13                          -cis-prostadienoic acid                                   1407  8β-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-13-trans-prost           enoic acid (Example 1358)                                                                     8β-methyl-9-oxo-15-hydroxy-6,7-dinor-10,13-trans                          -prostadienoic acid                                       1408  8α-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-8-iso-13-tran           sprostenoic acid (Example 1358)                                                               8α-methyl-9-oxo-15-hydroxy-6,7-dinor-8-iso-10,1                          3-trans-prostadienoic acid                                1409  8β-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-13-cis-prosten           oic acid (Example 1358)                                                                       8β-methyl-9-oxo-15-hydroxy-6,7-dinor-10,13-cis-p                          rostadienoic acid                                         1410  8α-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-8-iso-13-cis-           prostenoic acid (Example 1358)                                                                8α-methyl-9-oxo-15-hydroxy-6,7-dinor-8-iso-10,1                          3-cis-prostadienoic acid                                  1411  8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-trinor-20-methyl             13-trans-prostenoic acid (Example 1359)                                                       8β-methyl-9-oxo-15-hydroxy-5,6,7-trinor-20-methy                          l 10,13-trans-prostadienoic acid                          1412  8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-trinor-20-methyl-           8-iso-13-trans-prostenoic acid (Example 1359)                                                 8α-methyl-9-oxo-15-hydroxy-5,6,7-trinor-20-meth                          yl-8-iso-10,13-trans-prostadienoic acid                   1413  8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-trinor-20-methyl             13-cis-prostenoic acid (Example 1359)                                                         8β-methyl-9-oxo-15-hydroxy-5,6,7-trinor-20-methy                          l 10,13-cis-prostadienoic acid                            1414  8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-trinor-20-methyl-           8-iso-13-cis-prostenoic acid (Example 1359)                                                   8α-methyl-9-oxo-15-hydroxy-5,6,7-trinor-20-meth                          yl-8-iso-10,13-cis-prostadienoic -1415 8α-methy                          l-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-13-trans                          -prostenoic acid (Example 1360) 8β-methyl-9-oxo-                          15-hydroxy-7a,7b-bishomo-10,13-trans-prostadienoic                             acid                                                      1416  8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-8-iso-13-           trans-prostenoic acid (Example 1360)                                                          8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-                          10,13-trans-prostadienoic acid                            1417  8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-13-cis-pro           stenoic acid (Example 1360)                                                                   8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-10,13-c                          is-prostadienoic acid                                     1418  8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-8-iso-13-           cis-prostenoic acid (Example 1360)                                                            8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-                          10,13-cis-prostadienoic acid                              1419  8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-13-trans-prosten           oic acid (Example 1361)                                                                       8β-methyl-9-oxo-15-hydroxy-2-ethyl-10,13-trans-p                          rostadienoic acid                                         1420  8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-8-iso-13-trans-           prostenoic acid (Example 1361)                                                                8α-methyl-9-oxo-15-hydroxy-2-ethyl-8-iso-10,13-                          trans-prostadienoic acid                                  1421  8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-13-cis-prostenoi           c acid (Example 1361)                                                                         8β-methyl-9-oxo-15-hydroxy-2-ethyl-10,13-cis-pro                          stadienoic acid                                           1422  8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-8-iso-13-cis-pr           ostenoic acid (Example 1361)                                                                  8α-methyl-9-oxo-15-hydroxy-2-ehtyl-8-iso-10,13-                          cis-prostadienoic acid                                    1423  8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-trimethyl-13-tran           s-prostenoic acid (Example 1362)                                                              8β-methyl-9-oxo-15-hydroxy-3,3,20-trimethyl-10,1                          3-trans-prostadienoic acid                                1424  8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20-trimethyl-8-iso-           13-trans-prostenoic acid (Example 1362)                                                       8α-methyl-9-oxo-15-hydroxy-3,3,20-trimethyl-8-i                          so-10,13-trans-prostadienoic acid                         1425  8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-trimethyl-13-cis-           prostenoic acid (Example 1362)                                                                8β-methyl-9-oxo-15-hydroxy-3,3,20-trimethyl-10,1                          3-cis-prostadienoic acid                                  1426  8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20-trimethyl-8-iso-           13-cis-prostenoic acid (Example 1362)                                                         8α-methyl-9-oxo-15-hydroxy-3,3,20-trimethyl-8-i                          so-10,13-cis-prostadienoic acid                           1427  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxo-13-trans-prostenoi           c acid (Example 1363)                                                                         8β-methyl-9-oxo-15-hydroxy-3-oxa-10,13-trans-pro                          stadienoic acid                                           1428  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-8-iso-13-trans-pr           ostenoic acid (Example 1363)                                                                  8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-10,13,tr                          ans-prostadienoic acid                                    1429  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-13-cis-prostenoic            acid (Example 1363)                                                                           8β-methyl-9-oxo-15-hydroxy-3-oxa-10,13-cis-prost                          adienoic acid                                             1430  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-8-iso-13-cis-pros           tenoic acid (Example 1363)                                                                    8α-methyl-9-oxo-15-hydrxoy-3-oxa-8-iso-10,13-ci                          s-prostadienoic acid                                      1431  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-16,16-dimethyl-13-           trans-prostenoic acid (Example 1364)                                                          8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-                          10,13-trans-prostadienoic acid                            1432  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-16,16-dimethyl-8-           iso-13-trans-prostenoic acid (Example 1364)                                                   8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl                          -8-iso-10,13-trans-prostadienoic acid                     1433  8β-methyl-9-oxo-11α  ,15-dihydroxy-3-oxa-16,16-dimethyl-1           3-cis-prostenoic acid (Example 1364)                                                          8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-                          10,13-cis-prostadienoic acid                              1434  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-16,16-dimethyl-8-           iso-13-cis-prostenoic acid (Example 1364)                                                     8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl                          -8-iso-10,13-cis-prostadienoic acid                       1435  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-13-trans,17-cis-pr           ostadienoic acid (Example 1365)                                                               8β-methyl-9-oxo-15-hydroxy-3-oxa-10,13-trans,17-                          cis-prostatrienoic acid                                   1436  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-8-iso-13-trans,17           -cis-prostadienoic acid (Example 1365)                                                        8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-10,13-tr                          ans,17-cis-prostatrienoic acid                            1437  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-13-cis,-17-cis-pro           stadienoic acid (Example 1365)                                                                8β-methyl-9-oxo-15-hydroxy-3-oxa-10,13-cis,-17-c                          is-prostatrienoic acid                                    1438  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-8-iso-13-cis,17-c           is-prostadienoic acid (Example 1365)                                                          8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-10,13-ci                          s,17-cis-prostatrienoic acid                              1439  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-20-ethyl-13-trans-           prostenoic acid (Example 1366)                                                                8β-methyl-9-oxo-15-hydroxy-3-oxa-20-ethyl-10,13-                          trans-prostadienoic acid                                  1440  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-20-ethyl-8-iso-13           -trans-prostenoic acid (Example 1366)                                                         8α-methyl-9-oxo-15-hydroxy-3-oxa-20-ethyl-8-iso                          -10,13-trans-prostadienoic acid                           1441  8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-20-ethyl-13-cis-pr           ostenoic acid (Example 1366)                                                                  8β-methyl-9-oxo-15-hydroxy-3-oxa-20-ethyl-10,13-                          cis-prostadienoic acid                                    1442  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-20-ethyl-8-iso-13           -cis-prostenoic acid (Example 1366)                                                           8α-methyl-9-oxo-15-hydroxy-3-oxa-20-ethyl-8-iso                          -10,13-cis-prostadienoic acid                             1443  8β-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-dimethyl-           13-trans-prostenoic acid (Example 1367)                                                       8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimeth                          yl-10,13-trans-prostadienoic acid                         1444  8α-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-dimethyl           -8-iso-13-trans-prostenoic acid (Example 1367)                                                8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-diemt                          hyl-8-iso-10,13-trans-prostadienoic acid                  1445  8β-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-dimethyl-           13-cis-prostenoic acid (Example 1367)                                                         8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimeth                          yl-10,13-cis-prostadienoic acid                           1446  8α-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-diemthyl           -8-iso-13-cis-prostenoic acid (Example 1367)                                                  8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimet                          hyl-8-iso-10,13-cis-prostadienoic acid                    1447  8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-13-trans-prostenoi           c acid (Example 1368)                                                                         8β-methyl-9-oxo-15-hydroxy-7-nor-10,13-trans-pro                          stadienoic acid                                           1448  8α-methyl-9-oxo-11α,15-dihydroxy-7-nor-8-iso-13-trans-pr           ostenoic acid (Example 1368)                                                                  8α-methyl-9-oxo-15-hydroxy-7-nor-8-iso-10,13-tr                          ans-prostadienoic acid                                    1449  8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-13-cis-prostenoic            acid (Example 1368)                                                                           8β-methyl-9-oxo-15-hydroxy-7-nor-10,13-cis-prost                          adienoic acid                                             1450  8α-methyl-9-oxo-11α,15-dihydroxy-7-nor-8-iso-13-cis-pros           tenoic acid (Example 1368)                                                                    8α-methyl-9-oxo-15-hydroxy-7-nor-8-iso-10,13-ci                          s-prostadienoic acid                                      1451  8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo-16,16-dimethyl-1           3-trans-prostenoic acid (Example 1369)                                                        8β-methyl-9-oxo-15-hydroxy-7a-homo-16,16-dimethy                          l-10,13-trans-prostadienoic acid                          1452  8α-methyl-9-oxo-11α,15-dihydroxy-7a-homo-16,16-dimethyl-           8-iso-13-trans-prostenoic acid (Example 1369)                                                 8α-methyl-9-oxo-15-hydroxy-7a-homo-16,16-dimeth                          yl-8-iso-10,13-trans-prostadienoic acid                   1453  8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo-16,16-diemthyl-0           1,13-cis-prostadienoic acid (Example 1369)                                                    8β-methyl-9-oxo-15-hydroxy-7a-homo-16,16-dimethy                          l-10,13-cis-prostadienoic acid                            1454  8α-methyl-9-oxo-11α,15-dihydroxy-7a-homo-16,16-dimethyl-           8-iso-13-cis-prostenoic acid (Example 1369)                                                   8α-methyl-9-oxo-15-hydroxy-7a-homo-16,16-dimeth                          yl-8-iso-10,13-cis-prostadienoic acid                     1455  8β-methyl-9-oxo-11α,15-dihydroxy-2-phenyl-13-trans-proste           noic acid (Example 1370)                                                                      8β-methyl-9-oxo-15-hydroxy-2-phenyl-10,13-trans-                          prostadienoic acid                                        1456  8α-methyl-9-oxo-11α,15-dihydroxy-2-phenyl-8-iso-13-trans           -prostenoic acid (Example 1370)                                                               8α-methyl-9-oxo-15-hydroxy-2-phenyl-8-iso-10,13                          -trans-prostadienoic acid                                 1457  8β-methyl-9-oxo-11α,15-dihydroxy-2-phenyl-13-cis-prosteno           ic acid (Example 1370)                                                                        8β-methyl-9-oxo-15-hydroxy-2-phenyl-10,13-cis-pr                          ostadienoic acid                                          1458  8α-methyl-9-oxo-11α,15-dihydroxy-2-phenyl-8-iso-13-cis-p           rostenoic acid (Example 1370)                                                                 8α-methyl-9-oxo-15-hydroxy-2-phenyl-8-iso-10,13                          -cis-prostadienoic acid                                   1459  8β-methyl-9-oxo-11α,15-dihydroxy-2-methyl-13-trans,17-cis           -prostadienoic acid (Example 1371)                                                            8β-methyl-9-oxo-15-hydroxy-2-methyl-10,13-trans,                          17-cis-prostatrienoic acid                                1460  8α-methyl-9-oxo-11α,15-dihydroxy-2-methyl-8-iso-13-trans           ,17-cis-prostadienoic acid (Example 1371)                                                     8α-methyl-9-oxo-15-hydroxy-2-methyl-8-iso-10,13                          -trans,17-cis-prostatrienoic acid                         1461  8β-methyl-9-oxo-11α,15-dihydroxy-2-methyl-13-cis,17-cis-p           rostadionoic acid (Example 1371)                                                              8β-methyl-9-oxo-15-hydroxy-2-methyl-10,13-cis,17                          -cis-prostatrienoic acid                                  1462  8α-methyl-9-oxo-11α,15-dihydroxy-2-methyl-8-iso-13-cis-c           is,17-cis-prostadienoic acid (Example 1371)                                                   8α-methyl-9-oxo-15-hydroxy-2-methyl-8-iso-10,13                          -cis,17-cis-prostatrienoic acid                           1463  8β-methyl-9-oxo-11α,15-dihydroxy-5,cis,13-trans-prostadio           noic acid (Example 1372)                                                                      8β-methyl-9-oxo-15-hydroxy-5,cis,10,13-trans-pro                          statrienoic acid                                          1464  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-5,cis,13-trans-pr           ostadienoic acid (Example 1372)                                                               8α-methyl-9-oxo-15-hydroxy-8-iso-5,cis,10,13-tr                          ans-prostatrienoic acid                                   1465  8β-methyl-9-oxo-11α,15-dihydroxy-5,cis,13-cis-prostadieno           ic acid (Example 1372)                                                                        8β-methyl-9-oxo-15-hydroxy-5,cis,10,13-cis-prost                          atrienoic acid                                            1466  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-5,cis,13-cis-pros           tadienoic acid (Example 1372)                                                                 8α-methyl-9-oxo-15-hydroxy-8-iso-5,cis,10,13-ci                          s-prostatrienoic acid                                     1467  8β-methyl-9-oxo-11β,15-dihydro-xy-5-cis,13-trans,17-cis-pr           ostatrienoic acid (Example 1373)                                                              8β-methyl-9-oxo-15-hydroxy-5-cis,10,13-trans,                             17-cis-prostatetraeneoic acid                             1468  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-5-cis,-13-trans,1           7-cis-prostatrienoic acid (Example 1373)                                                      8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,10,-13-t                          rans,17-cis-prostatetraeneoic acid                        1469  8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,13-cis,-17-cis-pro           statrienoic acid (Example 1373)                                                               8β-methyl-9-oxo-15-hydroxy-5-cis,10,13-cis,-17-c                          is-prostatetraeneoic acid                                 1470  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-5-cis,-13-cis,17-           cisprostatrienoic acid (Example 1373)                                                         8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,10,-13-c                          is,17-cis-prostatetraeneoic acid                          1471  8β-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-5-cis,13-           trans-prostadienoic acid (Example 1374)                                                       8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-5-cis,                          10,13-trans-prostatrienoic acid                           1472  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-5-           cis,13-transprostadienoic acid (Example 1374)                                                 8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -5-cis,10,13-trans-prostatrienoic acid                    1473  8β-methyl-9-oxo-11α,15-dihydroxy-16,16-cis,13-cis-prostad           ienoic acid (Example 1374)                                                                    8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-5-cis-                          ,10,13-cis-prostatrienoic acid                            1474  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-5-           cis,13-cis-prostadienoic acid (Example 1374)                                                  8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -5-cis,10,13-cis-prostatrienoic acid                      1475  8β-methyl-9-oxo-11α,15,-dihydroxy-4-nor-20-methyl-5-cis-1           3-trans-prostadienoic acid (Example 1375)                                                     8β-methyl-9-oxo-15-hydroxy-4-nor-20-methyl-5-cis                          -10,13-trans-pro-statrienoic acid                         1476  8α-methyl-9-oxo-11α,15-dihydroxy-4-nor-20-methyl-8-iso-5           -cis,13-trans-prostadienoic acid (Example 1375)                                               8α-methyl-9-oxo-15-hydroxy-4-nor-20-methyl-8-is                          o-5-cis,10,13-trans-prostatrienoic acid                   1477  8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-20-methyl-5-cis-13           -cis-prostadienoic acid (Example 1375)                                                        8β-methyl-9-oxo-15-hydroxy-4-nor-20-methyl-5-cis                          ,10,13-cis-prostatrienoic acid                            1478  8α-methyl-9-oxo-11α,15-dihydro-4-nor-20-methyl-8-iso-5-c           is, 13-cisprostadienoic acid (Example 1375)                                                   8α-methyl-9-oxo-15-hydroxy-4-nor-20-methyl-8-is                          o-5-cis,10,13-cis-prostatrienoic acid                     1479  8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo-17,17-dimethyl-5           -cis,13-trans-prostadienoic acid (Example 1376)                                               8β-methyl-9-oxo-15-hydroxy-4a-homo-17,17-dimethy                          l-5-cis,10,13-trans-prostatrienoic acid                   1480  8α-methyl-9-oxo-11α,15-dihydroxy-4a-homo-17,17-dimethyl-           8-iso-5-cis,13-trans-prostadienoic acid (Example 1376)                                        8α-methyl-9-oxo-15-hydroxy-4a-homo-17,17-dimeth                          yl-8-iso-5-cis,10,13-trans-prostatrienoic acid            1481  8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo-17,17-dimethyl-5           -cis,13-cis-prostadienoic acid (Example 1376)                                                 8β-methyl-9-oxo-15-hydroxy-4a-homo-17,17-dimethy                          l-5-cis,10,13-cis-prostatrienoic acid                     1482  8α-methyl-9-oxo-11α,15-dihydroxy-4a-homo-17,17-dimethyl-           8-iso-5-cis,13-cis-prostadienoic acid (Example 1376)                                          8α-methyl-9-oxo-15-hydroxy-4a-homo-17,17-dimeth                          yl-8-iso-5-cis,10,13-cis-prostatrienoic acid              1483  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-20-ethyl-5           -cis,13-trans-prostadienoic acid (Example 1377)                                               8β-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-20-ethy                          l-5-cis,10,13-trans-prostatrienoic acid                   1484  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-20-ethyl-           8-iso-5-cis,13-trans-prostadienoic acid (Example 1377)                                        8α-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-20-eth                          yl-8-iso-5-cis,-10,13-trans-prostatrienoic acid           1485  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-20-ethyl-5           -cis,13-cis-prostadienoic acid (Example 1377)                                                 8β-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-20-ethy                          l-5-cis,10,13-cis-prostatrienoic acid                     1486  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-20-ethyl-           8-iso-5-cis,13-cis-prostadienoic acid (Example 1377)                                          8α-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-20-eth                          yl-8-iso-5-cis,-10,13-cis-prostatrienoic acid             1487  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-5-cis,13-t           rans,-17-cis-prostatrienoic acid (Example 1378)                                               8β-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-5-cis,1                          0,13-trans,17-cis-prostatetraenoic acid                   1488  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-8-iso-5-c           is,13-trans,17-cis-prostatrienoic acid                                                        8α-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-8-iso-                          5-cis,10,13-trans,17-cis-prostatetraenoic acid            1489  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-5-cis,13-c           is-17-cis-prostatrienoic acid (Example 1378)                                                  8β-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-5-cis,1                          0,13-cis-17-cis-prostatetraenoic acid acid                1490  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bishomo-8-iso-5-c           is,13-cis-17-cis-prostatrienoic acid (Example 1378)                                           8α-methyl-9-oxo-15-hydroxy-4a,4b-bishomo-8-iso-                          5-cis,10,13-cis-17-cis-prostatetraenoic acid              1491  methyl 8β-methyl-9-oxo-11α,15-dihydroxy-20-methyl-13-tran           s-prostenoate (Example 1379)                                                                  methyl 8β-methyl-9-oxo-15-hydroxy-20-methyl-10,1                          3-trans-prostadienoate                                    1492  methyl 8α-methyl-9-oxo-11α,15-dihydroxy-20-methyl-8-iso-           13-trans-prostenoate (Example 1379)                                                           methyl 8α-methyl-9-oxo-15-hydroxy-20-methyl-8-i                          so-10,13-trans-prostadienoate                             1493  methyl 8β-methyl-9-oxo-11α,15-dihydroxy-20-methyl-13-cis-           prostenoate (Example 1379)                                                                    methyl 8β-methyl-9-oxo-15-hydroxy-20-methyl-10,1                          3-cis-prostadienoate                                      1494  methyl 8α-methyl-9-oxo-11α,15-dihydroxy-20-methyl-8-iso-           13-cis-prostenoate (Example 1379)                                                             methyl 8α-methyl-9-oxo-15-hydroxy-20-methyl-8-i                          so-10,13-cis-prostadienoate                               1495  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-13-t           rans,17-cis-prostadienoate (Example 1380)                                                     ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-1                          0,13-trans,17-cis-prostatrienoate                         1496  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-8-i           so-13-trans,17-cis-prostadienoate (Example 1380)                                              ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-                          8-iso-10,13-trans,17-cis-prostatrienoate                  1497  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-13-c           is,17-cis-prostadienoate (Example 1380)                                                       ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-1                          0,13-cis,17-cis-prostatrienoate                           1498  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-8-i           so-13-cis,17-cis-prostadienoate (Example 1380)                                                ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-                          8-iso-10,13-cis,17-cis-prostatrienoate                    1499  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dime           thyl-13-trans-prostenoate (Example 1381)                                                      ethyl 8β-methyl-9-oxo-15-hydroxy-2-ethyl-16,16-d                          imethyl-10,13-trans-prostadienoate                        1500  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dim           ethyl-8-iso-13-trans-prostenoate (Example 1381)                                               ethyl 8α-methyl-9-oxo-15-hydroxy-2-ethyl-16,16-                          dimethyl-8-iso-10,13-trans-prostadienoate                 1501  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dime           thyl-13-cis-prostenoate (Example 1381)                                                        ethyl 8β-methyl-9-oxo-15-hydroxy-2-ethyl-16,16-d                          imethyl-10,13-cis-prostadienoate                          1502  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dim           ethyl-8-iso-13-cis-prostenoate (Example 1381)                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-2-ethyl-16,16-                          dimethyl-8-iso-10,13-cis-prostadienoate                   1503  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetramet           hyl-13-trans-prostenoate (Example 1382)                                                       ethyl 8β-methyl-9-oxo-15-hydroxy-3,3,17,17-tetra                          methyl-10,13-trans-prostadienoate                         1504  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetrame           thyl-8-iso-13-trans-prostenoate (Example 1382)                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3,3,17,17-tetr                          amethyl-8-iso-10,13-trans-prostadienoate                  1505  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetramet           hyl-13-cis-prostenoate (Example 1382)                                                         ethyl 8β-methyl-9-oxo-15-hydroxy-3,3,17,17-tetra                          methyl-10,13-cis-prostadienoate                           1506  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetrame           thyl-8-iso-13-cis-prostenoate (Example 1382)                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-3,3,17,17-tetr                          amethyl-8-iso-10,13-cis-prostadienoate                    1507  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimeth           yl-13-trans-prostenoate (Example 1383)                                                        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-17,17-dim                          ethyl-10,13-trans-prostadienoate                          1508  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimet           hyl-8-iso-13-trans-prostenoate (Example 1383)                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-17,17-di                          methyl-8-iso-10,13-trans-prostadienoate                   1509  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimeth           yl-13-cis-prostenoate (Example 1383)                                                          ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-17,17-dim                          ethyl-10,13-cis-prostadienoate                            1510  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimet           hyl-8-iso-13-cis-prostenoate (Example 1383)                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-17,17-di                          methyl-8-iso-10,13-cis-prostadienoate                     1511  butyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-trans-prostenoa           te (Example 1384)                                                                             butyl 8β-methyl-9-oxo-15-hydroxy-10,13-trans-pro                          stadienaote                                               1512  buty 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-trans-pro           stenoate (Example 1384)                                                                       butyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-tr                          ans-prostadienoate                                        1513  butyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoate            (Example 1384)                                                                               butyl 8β-methyl-9-oxo-15-hydroxy-13-cis-prostadi                          enoate                                                    1514  butyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-pros           tenoate (Example 1384)                                                                        butyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-ci                          s-prostadienoate                                          1515  decyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-trans,17-cis-pr           ostadienoate (Example 1385)                                                                   decyl 8β-methyl-9-oxo-15-hydroxy-10,13-trans,17-                          cis-prostatrienoate                                       1516  decyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-trans,17           -cis-prostadienoate (Example 1385)                                                            decyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-tr                          ans-,17-cis-prostatrienoate                               1517  decyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-17-cis-pros           tadienoate (Example 1385)                                                                     decyl 8α-methyl-9-oxo-15-hydroxy-10,13-cis-17-c                          is-prostatrienoate                                        1518  decyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-17-c           is-prostadienoate (Example 1385)                                                              decyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-ci                          s-17-cis-prostatrienoate                                  1519  ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hydroxy-13-trans-pro           stenoate (Example 1386)                                                                       ethyl 8β-methyl-9-oxo-15-hydroxy-10,13-trans-pro                          stadienoate                                               1520  ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hydroxy-8-iso-13-tr           ans-prostenoate (Example 1386)                                                                ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-tr                          ans-prostadienoate                                        1521  ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hydroxy-13-cis-prost           enoate (Example 1386)                                                                         ethyl 8β-methyl-9-oxo-15-hydroxy-10,13-ciss-pros                          tadienoate                                                1522  ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hydroxy-8-iso-13-ci           s-prostenoate (Example 1386)                                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-10,13-ci                          s-prostadienoate                                          ______________________________________                                    

EXAMPLES 1523 - 1654

Treatment of the designated 9-oxo-prostenoic acid and ester derivatives listed in Table 42 below with sodium borohydride in ethanol as described in Example 257 gives the product 9α and 9β hydroxy derivatives of the table, which are separable by standard chromatographic techniques.

                  TABLE 42                                                         ______________________________________                                               Starting 8-    Product                                                         methyl-9-oxo-  8-methyl-9α/β,-                                      11α,15-di-                                                                              11α,15-trihydroxy-                                  Ex-   hydroxy-13-prosten-                                                                           13-prostenoic                                             ample oic acid or ester                                                                             acid or ester                                             ______________________________________                                         1523  8β-methyl-prosta-glandin E.sub.1 (Example 1353)                                          8β-methyl-prosta-glandin F.sub.1 α/F.sub.1                           β                                                   1524  8α-methyl-8-iso-prostaglandin E.sub.1 (Example                                          8α-methyl-8-iso-prostaglandin                                            F.sub.1 α/F.sub.1 β                            1525  8β-methyl-9-oxo-11α-15-dihydroxy-13-cis-prostenoic acid             (Example 1353) 8β-methyl-9α/β,11α,-15-trihydro                          xy-13-cis-prostenoic acid                                 1526  8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic            acid (Example 1353)                                                                          8α-methyl-9α/β, 11α,                                    15-trihydroxy-8-iso-13-cis-prostenoic acid                1527  8β-methyl-9-oxo-11α, 15-dihydroxy-16,16-dimethyl-13-trans           -prostenoic acid (Example 1354)                                                               8β-methyl-9α/β,11α,-15-trihydro                          xy-16,16-dimethyl-13-trans-prostenoic acid                1528  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-13           -trans-prostenoic acid (Example 1354)                                                         8α-methyl-9α/β,11α,-15-trihydr                          oxy-16,16-dimethyl-8-iso-13-trans-prostenoic acid         1529  8β-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-13-,cis-p           rostenoic acid (Example 1354)                                                                 8β-methyl-9α/β,11α-15-trihydrox                          y-16,16-dimethyl-13-cis-prostenoic acid                   1530  8α-methyl-9-oxo-11α,15-dihydroxy-16,16-dimethyl-8-iso-13           -cis-prostenoic acid (Example 1354)                                                           8α-methyl-9α/β,11α,15-trihydro                          xy-16,16-dimethyl-8-iso-13-cis-prostenoic acid            1531  8β-methyl-9-oxo-11α-15-dihydroxy-17,17-dimethyl-13-trans-           prostenoic acid (Example 1355)                                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-17,17-dimethyl-13-trans-prostenoic acid                1532  8α-methyl-9-oxo-11α  ,15-dihydroxy-8-iso-17,17-di-methyl           -13-trans-prostenoic acid (Example 1355)                                                      8α-methyl-9α/β,11α,-15-trihydr                          oxy-17,17-dimethyl-8-iso-13-trans-prostenoic acid         1533  8β-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl-13-cis-pr           ostenoic acid (Example 1355)                                                                  8β-methyl-9α/β,11α,-15-trihydro                          xy-17,17-dimethyl-13-cis-prostenoic acid                  1534  8α-methyl-9-oxo-11α,15-dihydroxy-17,17-dimethyl-8-iso-13           -cis-prostenoic acid (Example 1355)                                                           8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-17,17-dimethyl-13-cis-prostenoic acid           1535  8β-methyl-9-oxo-11α-15-dihydroxy-13-trans-17-cis-prostadi           enoic acid (Example 1356)                                                                     8β-methyl-9α/β,11α-15-trihydrox                          y-13-trans,17-cis-prostadienoic acid                      1536  8α-methyl-9-oxo-11α-15-dihydroxy-8-iso-13-trans,17-cis-p           rostadienoic acid (Example 1356)                                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-13-trans-17-cis-prostadienoic acid              1537  8β-methyl-9-oxo-11α-15-dihydroxy-13-cis,17-cis-prostadien           oic acid (Example 1356)                                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-13-cis,17-cis-prostadienoic acid                       1538  8α-methyl-9-oxo-11α-15-dihydroxy-8-iso-13-trans-17-cis-p           rostadienoic acid (Example 1356)                                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-13-cis,17-cis-prostadienoic acid                1539  8β-methyl-9-oxo-11α-15-dihydroxy-20-ethyl-13-trans-proste           noic acid (Example 1357)                                                                      8β-methyl-9α/β,11α,-15-trihydro                          xy-20-ethyl-13-trans-prostenoic acid                      1540  8α-methyl-9-oxo-11α-15-dihydroxy-20-ethyl-8-iso-13-trans           -prostenoic acid (Example 1357)                                                               8α-methyl-9α/β,11α,-15-trihydr                          oxy-20-ethyl-8-iso-13-trans-prostenoic acid               1541  8β-methyl-9-oxo-11α-15-dihydroxy-20-ethyl-13-cis-prosteno           ic acid (Example 1357)                                                                        8β-methyl-9α/β,11α,-15-trihydro                          xy-20-ethyl-13-cis-prostenoic acid                        1542  8α-methyl-9-oxo-11α-15-dihydroxy-20-ethyl-8-iso-13-cis-p           rostenoic acid (Example 1357)                                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-20-ethyl-8-iso-13-cis-prostenoic acid                 1543  8β-methyl-9-oxo-11α,-15-dihydroxy-6,7-dinor-13-trans-pros           tenoic acid (Example 1358)                                                                    8β-methyl-9α/β,11α,-15-trihydro                          xy-6,7-dinor-13-trans-prostenoic acid                     1544  8α-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-8-iso-13-tran           s-prostenoic acid (Example 1358)                                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-6,7-dinor-8-iso-13-trans-prostenoic acid              1545  8β-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-13-cis-prosten           oic acid (Example 1358)                                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-6,7-dinor-13-cis-prostenoic acid                       1546  8α-methyl-9-oxo-11α,15-dihydroxy-6,7-dinor-8-iso-13-cis-           prostenoic acid (Example 1358)                                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-6,7-dinor-8-iso-13-cis-prostenoic acid                1547  8β-methyl-9-oxo-11α,-15-dihydroxy-5,6,7-trinor-20-methyl-           13-trans-prostenoic acid (Example 1359)                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-5,6,7-trinor-20-methyl-13-trans-prostenoic acid        1548  8α-methyl-9-oxo-11α,-15-dihydroxy-5,6,7-trinor-20-methyl           -8-iso-13-trans-prostenoic acid (Example 1359)                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-5,6,7-trinor-20-methyl-8-iso-13-trans-prostenoic                           acid                                                      1549  8β-methyl-9-oxo-11α-15-dihydroxy-5,6,7,-trinor-20-methyl-           13-cis-prostenoic acid (Example 1359)                                                         8β-methyl-9α/β,11α,-15-trihydro                          xy-5,6,7-trinor-20-methyl-13-cis-prostenoic acid          1550  8α-methyl-9-oxo-11α,-15-dihydroxy-5,6,7-trinor-20-methyl           -8-iso-13-cis-prostenoic acid (Example 1359)                                                  8α-methyl-9α/β,11α,-15-trihydr                          oxy-5,6,7-trinor-20-methyl-8-iso-13-cis-prostenoic                             acid                                                      1551  8β-methyl-9-oxo-11α,-15-dihydroxy-7a,7b-bishomo-13-trans-           prostenoic acid (Example 1360)                                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-7a,7b-bishomo-13-trans-prostenoic acid                 1552  8α-methyl-9-oxo-11α-15-dihydroxy-7a,7b-bishomo-8-iso-13-           trans-prostenoic acid (Example 1360)                                                          8α-methyl-9α/β,11α,-15-trihydr                          oxy-7a,7b-bishomo-8-iso-13-trans prostenoic acid          1553  8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bishomo-13-cis-pro           stenoic acid (Example 1360)                                                                   8β-methyl-9α/β,11α,15-trihydrox                          y-7a,7b-bishomo-13-cis-prostenoic acid                    1554  8α-methyl-9-oxo-11α,-15-dihydroxy-7a,7b-bishomo-8-iso-13           -cis-prostenoic acid (Example 1360)                                                           8α-methyl-9α/β,11α,-15-trihydr                          oxy-7a,7b-bishomo-8-iso-13-cis-prostenoic acid            1555  8β-methyl-9-oxo-11α,-15-dihydroxy-2-ethyl-13-trans-proste           noic acid (Example 1361)                                                                      8β-methyl-9α/β,11α,-15-trihydro                          xy-2-ethyl-13-trans-prostenoic acid                       1556  8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-8-iso-13-trans-           prostenoic acid (Example 1361)                                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-ethyl-8-iso-13-trans-prostenoic acid                1557  8β-methyl-9-oxo-11α,-15-dihydroxy-2-ethyl-13-cis-prosteno           ic acid (Example 1361)                                                                        8β-methyl-9α/β,11α,-15-trihydro                          xy-2-ethyl-13-cis-prostenoic acid                         1558  8α-methyl-9-oxo-11α,-15-dihydroxy-2-ethyl-8-iso-13-cis-p           rostenoic acid (Example 1361)                                                                 8α-methyl-9α/β,11α-15,trihydro                          xy-2-ethyl-8-iso-13-cis-prostenoic acid                   1559  8β-methyl-9-oxo-11α,-15-dihydroxy-3,3,20-trimethyl-8-iso-           13-trans-prostenoic acid (Example 1362)                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-3,3,20-trimethyl-13-trans-prostenoic acid              1560  8α-methyl-9-oxo-11α,-15-dihydroxy-3,3,20-trimethyl-8-iso           -13-trans-prostenoic acid (Example 1362)                                                      8β-methyl-9α/β,11α,-15-trihydro                          xy-3,3,20-trimethyl-8-iso-13-trans-prostenoic acid        1561  8β-methyl-9-oxo-11α,-15-dihydroxy-3,3,20-trimethyl-13-cis           -prostenoic acid (Example 1362)                                                               8β-methyl-9α/β,11α,-15-trihydro                          xy-3,3,20-trimethyl-13-cis-prostenoic acid                1562  8α-methyl-9-oxo-11α,-15-dihydroxy-3,3,20-trimethyl-8-iso           -13-cis-prostenoic acid (Example 1362)                                                        8α-methyl-9α/β,11α,-15-trihydr                          oxy-3,3,20-trimethyl-8-iso-13-cis-prostenoic acid         1563  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-13-trans-prosteno           ic acid (Example 1363)                                                                        8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-13-trans-prostenoic acid                         1564  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-8-iso-13-trans-p           rostenoic acid (Example 1363)                                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-8-iso-13-trans-prostenoic acid                  1565  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-8-iso-13-cis-pros           tenoic acid (Example 1363)                                                                    8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-8-iso-13-cis-prostenoic acid                     1566  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-8-iso-13-cis-pro           stenoic acid (Example 1363)                                                                   8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-8-iso-13-cis-prostenoic acid                    1567  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-16,16-dimethyl-13           -trans-prostenoic acid (Example 1364)                                                         8β-methyl-9α/β-11α,-15-trihydro                          xy-3-oxa-16,16-dimethyl-13-trans-prostenoic acid          1568  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-16,16-dimethyl-8           -iso-13-trans-prostenoic acid (Example 1364)                                                  8α-methyl-9α/β-11α,-5-trihydro                          xy-3-oxa-16,16-dimethyl-8-iso-13-trans-prostenoic                              acid                                                      1569  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-16,16-dimethyl-13           -cis-prostenoic acid (Example 1364)                                                           8β-methyl-9α/β-11α,-15-trihydro                          xy-3-oxa-16,16-dimethyl-13-cis-prostenoic acid            1570  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-16,16-dimethyl-8           -iso-13-cis-prostenoic acid (Example 1364)                                                    8α-methyl-9α/β-11α,-15-trihydr                          oxy-3-oxa-16,16-dimethyl-8-iso-13-cis-prostenoic                               acid                                                      1571  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-13-trans,17-cis-p           rostadienoic acid (Example 1365)                                                              8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-13-trans,17-cis-prostadienoic acid               1572  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-8-iso-13-trans,1           7-cis-prostadienoic acid (Example 1365)                                                       8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-8-iso-13-trans,17-cis-prostadienoic acid        1573  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-13-cis,17-cis-pro           stadienoic acid (Example 1365)                                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-13-cis,17-cis-prostadienoic acid                 1574  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-8-iso-13-cis,17-           cis-prostadienoic acid (Example 1365)                                                         8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-8-iso-13-cis,17-cis-prostadienoic acid          1575  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-20-ethyl-13-trans           -prostenoic acid (Example 1366)                                                               8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-20-ethyl-13-trans-prostenoic acid                1576  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-20-ethyl-8-iso-1           3-trans-prostenoic acid (Example 1366)                                                        8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-20-ethyl-8-iso-13-trans-prostenoic acid         1577  8β-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-20-ethyl-13-cis-p           rostenoic acid (Example 1366)                                                                 8β-methyl-9α/β,11α,-15-trihydro                          xy-3-oxa-20-ethyl-13-cis-prostenoic acid                  1578  8α-methyl-9-oxo-11α,-15-dihydroxy-3-oxa-20-ethyl-8-iso-1           3-cis-prostenoic acid (Example 1366)                                                          8α-methyl-9α/β,11α,-15-trihydr                          oxy-3-oxa-20-ethyl-8-iso-13-cis-prostenoic acid           1579  8β-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-dimethyl-           13-trans-prostenoic acid (Example 1367)                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-2-fluoro-17,17-dimethyl-13-trans-prostenoic acid       1580  8α-methyl-9-oxo-11α,15-dihydroxy-2-fluoro-17,17-dimethyl           -8-iso-13-trans-prostenoic acid (Example 1367)                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-fluoro-17,17-dimethyl-8-iso-13-trans-prostenoic                           acid                                                     1581  8β-methyl-9-oxo-11α,-15-dihydroxy-2-fluoro-17,17-dimethyl           -13-cis-prostenoic acid (Example 1367)                                                        8β-methyl 9α/β,11α,-15-trihydro                          xy-2-fluoro-17,17-dimethyl-13-cis-prostenoic acid         1582  8α-methyl-9-oxo-11α,-15-dihydroxy-2-fluoro-17,17-dimethy           l-8-iso-13-cis-prostenoic acid (Example 1367)                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-fluoro-17,17-dimethyl-8-iso-13-cis-prostenoic                            acid                                                      1583  8β-methyl-9-oxo-11α,-15-dihydroxy-7-nor-13-trans-prosteno           ic acid (Example 1368)                                                                        8β-methyl-9α/β,11α,-15-trihydro                          xy-7-nor-13-trans-prostenoic acid                         1584  8α-methyl-9-oxo-11α,-15-dihydroxy-7-nor-8-iso-13-trans-p           rostenoic acid (Example 1368)                                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-7-nor-8-iso-13-trans-prostenoic acid                  1585  8β-methyl-9-oxo-11α,-15-dihydroxy-7-nor-13-cis-prostenoic            acid (Example 1368)                                                                          8β-methyl-9α/β,11α,-15-trihydro                          xy-7-nor-13-cis-prostenoic acid                           1586  8α-methyl-9-oxo-11α,-15-dihydroxy-7-nor-8-iso-13-cis-pro           stenoic acid (Example 1368)                                                                   8α-methyl-9α/β,11α,-15-trihydr                          oxy-7-nor-8-iso-13-cis-prostenoic acid                    1587  8β-methyl-9-oxo-11α,-15-dihydroxy-7a-homo-16,16-dimethyl-           13-trans-prostenoic acid (Example 1369)                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-7a-homo-16,16-dimethyl-13-trans-prostenoic acid        1588  8α-methyl-9-oxo-11α,-15-dihydroxy-7a-homo-16,16-dimethyl           -8-iso-13-trans-prostenoic acid (Example 1369)                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-7a-homo-16,16-dimethyl-8-iso-13-trans-prostenoic                           acid                                                      1589  8β-methyl-9-oxo-11α,-15-dihydroxy-7a-homo-16,16-dimethyl-           13-cis-prostenoic acid (Example 1369)                                                         8β-methyl-9α/β,11α,-15-trihydro                          xy-7a-homo-16,16-dimethyl-13-cis-prostenoic acid          1590  8α-methyl-9-oxo-11α,-15-dihydroxy-7a-homo-16,16-dimethyl           -8-iso-13-cis-prostenoic acid (Example 1369)                                                  8α-methyl-9α/β,11α,-15-trihydr                          oxy-7a-homo-16,16-dimethyl-8-iso-13-cis-prostenoic                             acid                                                      1591  8β-methyl-9-oxo-11α,-15-dihydroxy-2-phenyl-13-trans-prost           enoic acid (Example 1370)                                                                     8β-methyl-9α/β,11α,-15-trihydro                          xy-2-phenyl-13-trans-prostenoic acid                      1592  8α-methyl-9-oxo-11α,-15-dihydroxy-2-phenyl-8-iso-13-tran           s-prostenoic acid (Example 1370)                                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-phenyl-8-iso-13-trans-prostenoic acid               1593  8β-methyl-9-oxo-11α,-15-dihydroxy-2-phenyl-13-cis-prosten           oic acid (Example 1370)                                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-2-phenyl-13-cis-prostenoic acid                        1594  8α-methyl-9-oxo-11α,-15-dihydroxy-2-phenyl-8-iso-13-cis-           prostenoic acid (Example 1370)                                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-phenyl-8-iso-13-cis-prostenoic acid                 1595  8β-methyl-9-oxo-11α,-15-dihydroxy-2-methyl-13-trans-17-ci           s-prostadienoic acid (Example 1371)                                                           8β-methyl-9α/β,11α,-15-trihydro                          xy-2-methyl-13-trans,17-cis-prostadienoic acid            1596  8α-methyl-9-oxo-11α,-15-dihydroxy-2-methyl-8-iso-13-tran           s,17-cis-prostadienoic acid (Example 1371)                                                    8α-methyl-9α/β,11α-15-trihydro                          xy-2-methyl-8-iso-13 cis-acid                             1597  8β-methyl-9-oxo-11α,-15-dihydroxy-2-methyl-13-cis,17-cis-           prostadienoic acid (Example 1371)                                                             8β-methyl-9α/β,11α,-15-trihydro                          xy-2-methyl-13-cis,17-cis-prostadienoic acid              1598  8α-methyl-9-oxo-11α,-15-dihydroxy-2-methyl-8-iso-13-cis,           17-cis-prostadienoic acid (Example 1371)                                                      8α-methyl-9α/β,11α,-15-trihydr                          oxy-2-methyl-8-iso-13-cis,17-cis-prostadienoic acid       1599  8β-methyl-9-oxo-11α,-15-dihydroxy-5,cis,-13-trans-prostad           ienoic acid (Example 1372)                                                                    8β-methyl-9α/β,11α,-15-trihydro                          xy-5 cis -13-trans-prostadienoic acid                     1600  8α-methyl-9-oxo-11α,-15-dihydroxy-8-iso-5-cis-13-trans-p           rostadienoic acid (Example 1372)                                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-5 cis,13-trans-prostadienoic acid               1601  8β-methyl-9-oxo-11α,-15-dihydroxy-5-cis,13-cis-prostadien           oic acid (Example 1372)                                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-5 cis -13-cis-prostadienoic acid                       1602  8α-methyl-9-oxo-11α,-15-dihydroxy-8-iso-5-cis-13-cis-pro           stadienoic acid (Example 1372)                                                                8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-5-cis-13-cis-prostadienoic acid                 1603  8β-methyl-9-oxo-11α,-15-dihydroxy-5-cis,-13-trans,17-cis-           prostatrienoic acid (Example 1373)                                                            8β-methyl-9α/β,11α,-15-trihydro                          xy-5-cis,-13-trans,17-cis-                                1604  8α-methyl-9-oxo-11α,-15-dihydroxy-8-iso-5-cis,13-trans,1           7-cis-prostatrienoic acid (Example 1373)                                                      8α-methyl-9α/β,11α,-15-dihydro                          xy-8-iso-5-cis,13-trans,17-cis-prostatrienoic acid        1605  8β-methyl-9-oxo-11α,-15-dihydroxy-5-cis,-13-cis,17-cis-pr           ostatrienoic acid (Example 1373)                                                              8β-methyl-9α/β,11α,-15-trihydro                          xy-5-cis,13-cis,17-cis-prostatrienoic acid                1606  8α-methyl-9-oxo-11α,-15-dihydroxy-8-iso-5-cis,13-cis,17-           cis-prostatrienoic acid (Example 1373)                                                        8α-methyl-9α/β,11α,-15-trihydr                          oxy-8-iso-5-cis,13-cis,17-cis-prostatrienoic acid         1607  8β-methyl-9-oxo-11α,-15-dihydroxy-16,16-dimethyl-5-cis,13           -trans-prostadienoic (Example 1374)                                                           8β-methyl-9α/β,11α,-15-trihydro                          xy-16,16-dimethyl-5-cis,13-trans-prostadienoic acid       1608  8α-methyl-9-oxo-11α,-15-dihydroxy-16,16-dimethyl-8-iso-5           -cis,13-trans-prostadienoic acid (Example 1374)                                               8α-methyl-9α/β,11α,-15-trihydr                          oxy-16,16-dimethyl-8-iso-5-cis-13-transprostadienoic                           acid                                                      1609  8β-methyl-9-oxo-11α,-15-dihydroxy-16,16-dimethyl-5-cis              13-cis-prostadienoic acid (Example 1374)                                                      8β-methyl-9α/β,11α,-15-trihydro                          xy-16,16-dimethyl-5-cis,13-cis-prostadienoic acid         1610  8α-methyl-9-oxo-11α,-15-dihydroxy-16,16-dimethyl-8-iso-5           -cis-13-cis-prostadienoic acid (Example 1374)                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-16,16-dimethyl-8-iso-5-cis-13-cis-prostadienoic                            acid                                                      1611  8β-methyl-9-oxo-11α,-15-dihydroxy-4-nor-20-methyl-5-cis,1           3-trans-prostadienoic acid (Example 1375)                                                     8β-methyl-9α/β,11α,-15-trihydro                          xy-4-nor-20-methyl-5-cis,13-trans-prostadienoic                                acid                                                      1612  8α-methyl-9-oxo-11α,-15-dihydroxy-4-nor-20-methyl-8-iso-           5-cis,13-trans-prostadienoic acid (Example 1375)                                              8α-methyl-9α/β,11α,-15-trihydr                          oxy-4-nor-20-methyl-8-iso-5-cis,13-trans-prostadienoi                          c acid                                                    1613  8β-methyl-9-oxo-11α,-15-dihydroxy-4-nor-20-methyl-5-cis,1           3-cis-prostadienoic acid (Example 1375)                                                       8β-methyl-9α/β,11α,-15-trihydro                          xy-4-nor-20-methyl-5-cis,13-cis-prostadienoic acid        1614  8α-methyl-9-oxo-11α,-15-dihydroxy-4-nor-20-methyl-8-iso-           5-cis,13-cis-prostdienoic acid (Example 1375)                                                 8α-methyl-9α/β,11α,-15-trihydr                          oxy-4-nor-20-methyl-8-iso-5-cis,13-cis-prostadinoic                            acid                                                      1615  8β-methyl-9-oxo-11α  ,-15-dihydroxy-4a-homo-17,17-dimethy           l-5-cis-13-trans-prostadienoic acid (Example 1376)                                            8β-methyl-9α/β,11α,-15-trihydro                          xy-4a-homo-17,17-dimethyl-5-cis,13-trans-prostadienoi                          c acid                                                    1616  8α-methyl-9-oxo-11α,-15-dihydroxy-4a-homo-17,17-dimethyl           -8-iso-5-cis,13-trans-prostadienoic acid (Example                                             8α-methyl-9α/β,11α,-15-trihydr                          oxy-4a-homo-17,17-dimethyl-8-iso-5-cis,13-cis-prostad                          ienoic acid                                               1617  8β-methyl-9-oxo-11α,-15-dihydroxy-4a-homo-17,17-dimethyl-           5-cis-13-cis-prostadienoic acid (Example 1376)                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-4a-homo-17,17-dimethyl-5-cis,13-cis-prostadienoic                           acid                                                      1618  8α-methyl-9-oxo-11α,-15-dihydroxy-4a-homo-17,17-dimethyl           -8-iso-5-cis,13-cis-prostadienoic acid (Example 1376)                                         8α-methyl-9α/β,11α,-15-trihydr                          oxy-4a-homo-17,17-dimethyl-8-iso-5-cis,13-cis-prostad                          ienoic acid                                               1619  8β-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bishomo-20-ethyl-           5-cis,13-trans-prostadienoic acid (Example 1377)                                              8β-methyl-9α/β,11α,-15-trihydro                          xy-4a,4b-bishomo-20-ethyl-5-cis,13-trans-prostadienoi                          c acid                                                    1620  8α-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bishomo-20-ethyl           -8-iso-5-cis,13-trans-prostadienoic acid (Example                                             8α-methyl-9α/β,11α,-15-trihydr                          oxy-4a,4b-bishomo-20-ethyl-8-iso-5-cis,13-trans-prost                          adienoic acid                                             1621  8β-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bishomo-20-ethyl-           5-cis,13-cis-prostadienoic acid (Example 1377)                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-4a,4b-bishomo-20-ethyl-5-cis,13-cis-prostadienoic                           acid                                                      1622  8α-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bishomo-20-ethyl           -8-iso-5-cis,13-cis-prostadienoic acid (Example 1377)                                         8α-methyl-9α/β,11α,-15-trihydr                          oxy-4a,4b-bishomo-20-ethyl-8-iso-5-cis,13-cis-prostad                          ienoic                                                    1623  8β-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bis-homo-5-cis,13           -trans,17-cis-prostatrienoic acid (Example 1378)                                              8β-methyl-9α/β,11α,-15-trihydro                          xy-4a,4b-bishomo-5-cis,13-trans,17-cis-prostatrienoic                           acid                                                     1624  8α-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bis-homo-8-iso-5           -cis-13-trans,17-cis-prostatrienoic acid (Example                                             8α-methyl-9α/β,11α,-15-trihydr                          oxy-4a,4b-bis-homo-8-iso-5-cis,-13-trans,17-cis-prost                          atrienoic acid                                            1625  8β-methyl-9-oxo-11α,-15-dihydroxy-4a,4b-bis-homo-5-cis,13           -cis,17-cis-prostatrienoic acid (Example 1378)                                                8β-methyl-9α/β,11α,-15-trihydro                          xy-4a,4b-bis-homo-5-cis,13-cis-17-cis-prostatrienoic                           acid                                                      1626  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-bis-homo-8-iso-5-           cis,13-cis-17-cis-prostatrienoic acid (Example 1378)                                          8α-methyl-9α/β,11α,15-trihydro                          xy-4a,4b-bis-homo-8-iso-5-cis,13-cis,17-cis-prostatri                          enoic acid                                                1627  methyl 8β-methyl-9-oxo-11α,15-dihydroxy-20-methyl-13-tran           s-prostenoate (Example 1379)                                                                  methyl 8β-methyl-9α/β,11α,15-tr                          ihydroxy-20-methyl-13-trans-prostenoate                   1628  methyl 8α-methyl-9-oxo-11α,15-dihydroxy-20-methyl-8-iso-           13-trans-prostenoate (Example 1379)                                                           methyl 8α-methyl-9α/β,11α,15-t                          rihydroxy-20-methyl-8-iso-13-trans-prostenoate            1629  methyl 8β-methyl-9-oxo-11α,15-dihydroxy-20-methyl-13-cis-           prostenoate (Example 1379)                                                                    methyl 8β-methyl-9α/β,11α,15-tr                          ihydroxy-20-methyl-13-cis-prostenoate                     1630  methyl 8α-methyl-9-oxo-11α,15-dihydroxy-20-methyl-8-iso-           13-cis-prostenoate (Example 1379)                                                             methyl 8α-methyl-9α /β,11α,15-                          trihydroxy-20-methyl-8-iso-13-cis-prostenoate             1631  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bis-homo-13-           trans,17-cis-prostadienoate (Example 1380)                                                    ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-7a,7b-bis-homo-13-trans,17-cis-prostadienoate                          5                                                         1632  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bis-homo-8-           iso-13-trans,17-cis-prostadienoate (Example 1380)                                             ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-7a,7b-bis-homo-8-iso-13-trans,17-cis-prostad                          ienoate                                                   1633  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bis-homo-13-           cis-17-cis-prostadienoate (Example 1380)                                                      ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-7a,7b-bis-homo-13-cis,17-cis-prostadienoate       1634  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-bis-homo-8-           iso-13-cis,17-cis-prostadienoate (Example 1380)                                               ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-7a,7b-bis-homo-8-iso-13-cis-17-cis-prostadie                          noate                                                     1635  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dime           thyl-13-trans-prostenoate (Example 1381)                                                      ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-2-ethyl-16,16-dimethyl-13-trans-prostenoate       1636  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dim           ethyl-8-iso-13-trans-prostenoate (Example 1381)                                               ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-2-ethyl-16,16-dimethyl-8-iso-13-trans-proste                          noate                                                     1637  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl-16,16-dime           thyl-13-cis-prostenoate (Example 1381)                                                        ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-2-ethyl-16,16-dimethyl-13-cis-prostenoate         1638  ethyl 8α-methyl-9-oxo-11α,11α,15-dihydroxy-2-ethyl           -16,16-dimethyl-8-iso-13-cis-prostenoate (Example                                             ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-2-ethyl-16,16-dimethyl-8-iso-13-cis-prosteno                          ate                                                       1639  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetramet           hyl-13-trans-prostenoate (Example 1382)                                                       ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-3,3,17,17-tetramethyl-13-trans-prostenoate        1640  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetrame           thyl-8-iso-13-trans-prostenoate (Example 1382)                                                ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-3,3,17,17-tetramethyl-8-iso-13-trans-prosten                          oate                                                      1641  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetramet           hyl-13-cis-prostenoate (Example 1382)                                                         ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-3,3,17,17-tetramethyl-13-cis-prostenoate          1642  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,17,17-tetrame           thyl-8-iso-13-cis-prostenoate (Example 1382)                                                  ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-3,3,17,17-tetramethyl-8-iso-13-cis-prostenoa                          te                                                        1643  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimeth           yl-13-trans-prostenoate (Example 1383)                                                        ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-3-oxa-17,17-dimethyl-13-trans-prostenoate         1644  ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimet           hyl-8-iso-13-trans-prostenoate (Example 1383)                                                 ethyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-3-oxa-17,17-dimethyl-8-iso-13-trans-prosteno                          ate                                                       1645  ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-17,17-dimeth           yl-13-cis-prostenoate (Example 1383)                                                          ethyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-3-oxa-17,17-dimethyl-13-cis-prostenoate           1646  ethyl 8α-methyl-9-oxo-11α-15-dihydroxy-3-oxa-17,17-dimet           hyl-8-iso-13-cis-prostenoate (Example 1383)                                                   ethyl 8α-methyl-9α/β,11α-15-tr                          ihydroxy-3-oxa-17,17-dimethyl-8-iso-13-cis-prostenoat                          e                                                         1647  butyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-trans-prostenoa           te (Example 1384)                                                                             butyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-13-trans-prostenoate                              1648  butyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-transpro           stenoate (Example 1384)                                                                       butyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-8-iso-13-trans-prostenoate                       1649  butyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoate            (Example 1384)                                                                               butyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-13-cis-prostenoate                                1650  butyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-pros           tenoate (Example 1384)                                                                        butyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-8-iso-13-cis-prostenoate                         1651  decyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-trans,17-cis-pr           ostadienoate (Example 1385)                                                                   decyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-13-trans,17-cis-prostadienoate                    1652  decyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-trans,17           -cis-prostadienoate (Example 1385)                                                            decyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-8-iso-13-trans,17-cis-prostadienoate             1653  decyl 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis,17-cis-pros           tadienoate (Example 1385)                                                                     decyl 8β-methyl-9α/β,11α,15-tri                          hydroxy-13-cis,17-cis-prostadienoate                      1654  decyl 8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis,17-c           is-prostadienoate (Example 1385)                                                              decyl 8α-methyl-9α/β,11α,15-tr                          ihydroxy-8-iso-13-cis,17-cis-prostadienoate               ______________________________________                                    

EXAMPLES 1655-1781

Saponification of the alkyl esters designated in Table 43 below by the procedure described in Example 495 is productive of the carboxylic acids of the table. The epimeric 9α and 9β hydroxy products are separable by the usual chromatographic procedures.

                  TABLE 43                                                         ______________________________________                                         Ex-   Starting alkyl                                                           ample prostenoate    Product prostenoic acid                                   ______________________________________                                         1655  11-deoxy-8β-methyl-prostaglandin E.sub.1 methyl ester (Example            1188)          11-deoxy-8β-methyl-prostaglandin E.sub.1             1656  11-deoxy-8α-methyl-8-iso-prostaglandin E.sub.1 methyl ester              (Example 1188) 11-deoxy-8α-methyl-8-iso-prostaglandin                                   E.sub.1                                                   1657  methyl 15-hydroxy-8β-methyl 9-oxo-13-cis-prostenoate (Example             1188)          15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoic                              acid                                                      1658  methyl-15-hydroxy-8α-methyl-8-iso-9-oxo-13-cis-prostenoate               (Example 1188) 15-hydroxy-8α-methyl-8-iso-9-oxo-13-cis-prosten                          oic acid                                                  1659  11-deoxy-8β-methyl-prostaglandin F.sub.1 α/β methyl            esters (Ex. 1206)                                                                             11-deoxy-8β-methyl-prostaglandin F.sub.1                                  α/β                                            1660  11-deoxy-8α-methyl-8-iso-prostaglandin F.sub.1 α/β            methyl esters (Example 1207)                                                                  11-deoxy-8α-methyl-8-iso-prostaglandin F.sub.1                           α/β                                            1661  methyl 9α,15-dihydroxy-8β-methyl-13-cis-prostenoate                 (Example 1208) 9α,15-dihydroxy-8β-methyl-13-cis-prostenoi                          c acid                                                    1662  ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-13-trans-proste           noate (Example 1190)                                                                          8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-13-tra                          ns-prostenoic acid                                        1663  ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso-13-trans           -prostenoate (Example 1190)                                                                   8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -13-trans-prostenoic acid                                 1664  ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-13-cis-prosteno           ate (Example 1190)                                                                            8β-methyl-9-oxo-15-hydroxy-16,16-dimethyl-13-cis                          -prostenoic acid                                          1665  ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso-13-cis-p           rostenoate (Example 1190)                                                                     8α-methyl-9-oxo-15-hydroxy-16,16-dimethyl-8-iso                          -13-cis-prostenoic acid                                   1666  ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-trans-proste           noate (Example 1191)                                                                          8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-tra                          ns-prostenoic acid                                        1667  ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso-13-trans           -prostenoate (Example 1191)                                                                   8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso                          -13-trans-prostenoic acid                                 1668  ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-cis-prosteno           ate (Example 1191)                                                                            8β-methyl-9-oxo-15-hydroxy-17,17-dimethyl-13-cis                          -prostenoic acid                                          1669  ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso-13-cis-p           rostenoate (Example 1191)                                                                     8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso                          -13-cis-prostenoic acid                                   1670  ethyl 8β-methyl-9-oxo-15-hydroxy-13-trans,17-cis-prostadienoate            (Example 1192)                                                                               8β-methyl-9-oxo-15-hydroxy-13-trans,17-cis-prost                          adienoic acid                                             1671  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-trans,17-cis-prostad           ienoate (Example 1192)                                                                        8α-methyl-9-oxo-15-hydroxy-8-iso-13-trans,17-ci                          s-prostadienoic acid                                      1672  ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,17-cis-prostadienoate             (Example 1192) 8β-methyl-9-oxo-15-hydroxy-13-cis,17-cis-prostad                          ienoic acid                                               1673  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-cis,17-cis-prostadie           noate (Example 1192)                                                                          8α-methyl-9-oxo-15-hydroxy-8-iso-13-cis,17-cis-                          prostadienoic acid                                        1674  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-trans-prostenoate            (Example 1193) 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-trans-pro                          stenoic acid                                              1675  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-trans-prost           enoate (Example 1193)                                                                         8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-tr                          ans-prostenoic acid                                       1676  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-cis-prostenoate              (Example 1193) 8β-methyl-9-oxo-15-hydroxy-20-ethyl-13-cis-prost                          enoic acid                                                1677  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-cis-prosten           oate (Example 1193)                                                                           8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-13-ci                          s-prostenoic acid                                         1678  ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-13-trans-prosten           oate (Example 1195)                                                                           8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-13-tran                          s-prostenoic acid                                         1679  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-13-trans-           prostenoate (Example 1195)                                                                    8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-                          13-trans-prostenoic acid                                  1680  ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-13-cis-prostenoa           te (Example 1195)                                                                             8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-13-cis-                          prostenoic acid                                           1681  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-13-cis-pr           ostenoate (Example 1195)                                                                      8α-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-8-iso-                          13-cis-prostenoic acid                                    1682  ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bisethyl-13-trans-prosten           oate (Example 1196)                                                                           8β-methyl-9-oxo-15-hydroxy-2,20-bisethyl-13-tran                          s-prostenoic acid                                         1683  ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-bisethyl-8-iso-13-trans-           prostenoate (Example 1196)                                                                    8α-methyl-9-oxo-15-hydroxy-2,20-bisethyl-8-iso-                          13-trans-prostenoic acid                                  1684  ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-bisethyl-13-cis-prostenoa           te (Example 1196)                                                                             8β-methyl-9-oxo-15-hydroxy-2,20-bisethyl-13-cis-                          prostenoic acid                                           1685  ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-bisethyl-8-iso-13-cis-pr           ostenoate (Example 1196)                                                                      8α-methyl-9-oxo-15-hydroxy-2,20-bisethyl-8-iso-                          13-cis-prostenoic acid                                    1686  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-13-trans-           prostenoate (Example 1197)                                                                    8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-                          13-trans-prostenoic acid                                  1687  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-8-iso-13           -trans-prostenoate (Example 1197)                                                             8α-methyl-9-oxo-15-hydroxy-15-oxa-16,16-dimethy                          l-8-iso-13-trans-prostenoic acid                          1688  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-13-cis-pr           ostenoate (Example 1197)                                                                      8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-                          13-cis-prostenoic acid                                    1689  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-8-iso-13           -cis-prostenoate (Example 1197)                                                               8α-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl                          -8-iso-13-cis-prostenoic acid                             1690  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-13-trans,16-cis-prostadi           enoate (Example 1198)                                                                         8β-methyl-9-oxo-15-hydroxy-3-oxa-13-trans,17-cis                          -prostadienoic acid                                       1691  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-trans,17-cis-p           rostadienoate (Example 1198)                                                                  8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-trans                          ,17-cis-prostadienoic acid                                1692  ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-13-cis,17-cis-prostadien           oate (Example 1198)                                                                           8β-methyl-9-oxo-15-hydroxy-3-oxa-13-cis,17-cis-p                          rostadienoic acid                                         1693  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-cis,17-cis-pro           stadienoate (Example 1198)                                                                    8α-methyl-9-oxo-15-hydroxy-3-oxa-8-iso-13-cis,1                          7-cis-prostadienoic acid                                  1694  ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-trans-prost           enoate (Example 1199)                                                                         8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-tr                          ans-prostenoic acid                                       1695  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-iso-13-tran           s-prostenoate (Example 1199)                                                                  8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-is                          o-13-trans-prostenoic acid                                1696  ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-cis-prosten           oate (Example 1199)                                                                           8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-13-ci                          s-prostenoic acid                                         1697  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-iso-13-cis-           prostenoate (Example 1199)                                                                    8α-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-8-is                          o-13-cis-prostenoic acid                                  1698  ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-13-tra           ns-prostenoate (Example 1200)                                                                 8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimeth                          yl-13-trans-prostenoic acid                               1699  ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-8-iso           -13-trans-prostenoate (Example 1200)                                                          8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimet                          hyl-8-iso-13-trans-prostenoic acid                        1700  ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimethyl-13-cis           -prostenoate (Example 1200)                                                                   8β-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimeth                          yl-13-cis-prostenoic acid                                 1701  ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-dimethyl-8-iso-13-cis-p           rostenoate (Example 1200)                                                                     8α-methyl-9-oxo-15-hydroxy-2-fluoro-17,17-dimet                          hyl-8-iso-13-cis-prostenoic acid                          1702  ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-trans-prostenoate            (Example 1201) 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-trans-pro                          stenoic acid                                              1703  ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-trans-prote           noate (Example 1201)                                                                          8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-tr                          ans-prostenoic acid                                       1704  ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-cis-prostenoate              (Example 1201) 8β-methyl-9-oxo-15-hydroxy-10a-homo-13-cis-prost                          enoic acid                                                1705  ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-cis-prosten           oate (Example 1201)                                                                           8α-methyl-9-oxo-15-hydroxy-10a-homo-8-iso-13-ci                          s-prostenoic acid                                         1706  ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13-trans-pr           ostenoate (Example 1202)                                                                      8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13                          -trans-prostenoic acid                                    1707  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8-iso-13-t           rans-prostenoate (Example 1202)                                                               8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8                          -iso-13-trans-prostenoic acid                             1708  ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13-cis-pros           tenoate (Example 1202)                                                                        8β-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-13                          -cis-prostenoic acid                                      1709  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8-iso-13-c           is-prostenoate (Example 1202)                                                                 8α-methyl-9-oxo-15-hydroxy-2-phenyl-20-methyl-8                          -iso-13-cis-prostenoic acid                               1710  methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostat           rienoate (Example 1203)                                                                       8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans,17-cis                          -prostatrienoic acid                                      1711  methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans,17-cis-           prostatrienoate (Example 1203)                                                                8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans                          ,17-cis-prostatrienoic acid                               1712  methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis,17-cis-prostatri           enoate (Example 1203)                                                                         8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis,                                  17-cis-prostatrienoic acid                                1713  methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis,17-cis-pr           ostatrienoate (Example 1203)                                                                  8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis,1                          7-cis-prostatrienoic acid                                 1714  ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans-prostadienoate            (Example 1204) 8β-methyl-9-oxo-15-hydroxy-5-cis,13-trans-prosta                          dienoic acid                                              1715  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans-prostadi           enoate (Example 1204)                                                                         8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-trans                          -prostadienoic acid                                       1716  ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis-prostadienoate              (Example 1204) 8β-methyl-9-oxo-15-hydroxy-5-cis,13-cis-prostadi                          enoic acid                                                1717  ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis-prostadien           oate (Example 1204)                                                                           8α-methyl-9-oxo-15-hydroxy-8-iso-5-cis,13-cis-p                          rostadienoic acid                                         1718  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-trans-prosta           dienoate (Example 1205)                                                                       8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-tra                          ns-prostadienoic acid                                     1719  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis,13-trans           -prostadienoate (Example 1205)                                                                8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis                          ,13-trans-prostadienoic acid                              1720  ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-cis-prostadi           enoate (Example 1205)                                                                         8β-methyl-9-oxo-15-hydroxy-20-ethyl-5-cis,13-cis                          -prostadienoic acid                                       1721  ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis,13-cis-p           rostadienoate (Example 1205)                                                                  8α-methyl-9-oxo-15-hydroxy-20-ethyl-8-iso-5-cis                          ,13-cis-prostadienoic acid                                1722  1210           8β-methyl-9α/β,15-dihydroxy-16,16-dim                          ethyl-13-trans-prostenoic acid                            1723  1211           8α-methyl-9α/β,15-dihydroxy-16,16-di                          methyl-8-iso-13-trans-prostenoic acid                     1724  1212           8β-methyl-9α/β,15-dihydroxy-16,16-dim                          ethyl-3-cis-prostenoic acid                               1725  1213           8α-methyl-9α,β,15-dihydroxy-16,16-di                          methyl-8-iso-13-cis-prostenoic acid                       1726  1214           8β-methyl-9α/β,15-dihydroxy-17,17-dim                          ethyl-13-trans-prostenoic acid                            1727  1215           8α-methyl-9α/β,15-dihydroxy-17,17-di                          methyl-8-iso-13-trans-prostenoic acid                     1728  1216           8β-methyl-9α/β,15-dihydroxy-17,17-dim                          ethyl-13-cis-prostenoic acid                              1729  1217           8α-methyl-9α/β,15-dihydroxy-17,17-di                          methyl-8-iso-13-cis-protenoic acid                        1730  1218           8β-methyl-9α/β,15-dihydroxy-13-trans,                          17-cis-prostadienoic acid                                 1731  1219           8α-methyl-9α/β,15-dihydroxy-8-iso-13                          -trans,17-cis-prostadienoic acid                          1732  1220           8β-methyl-9α/β,15-dihydroxy-13-cis,17                          -cis-prostadienoic acid                                   1733  1221           8α-methyl-9α/β,15-dihydroxy-8-iso-13                          -cis,17-cis-prostadienoic acid                            1734  1222           8β-methyl-9α/β,15-dihydroxy-20-ethyl-                          13-trans-prostenoic acid                                  1735  1223           8α-methyl-9α/β,15-dihydroxy-20-ethyl                          -8-iso-13-trans-prostenoic acid                           1736  1224           8β-methyl-9α/β,15-dihydroxy-20-ethyl-                          13-cis-prostenoic acid                                    1737  1225           8α-methyl-9α/β,15-dihyroxy-20-ethyl-                          8-iso-13-cis-prostenoic acid                              1738  1230           8β-methyl-9α/β,15-dihydroxy-7a,7b-bis                          homo-13-trans-prostenoic acid                             1739  1231           8α-methyl-9α/β,15-dihydroxy-7a,7b-bi                          shomo-8-iso-13-trans-prostenoic acid                      1740  1232           8β-methyl-9α/β,15-dihydroxy-7a,7b-bis                          homo-13-cis-prostenoic acid                               1741  1233           8α-methyl-9α/β,15-dihydroxy-7a,7b-bi                          shomo-8-iso-13-cis-prostenoic acid                        1742  1234           8β-methyl-9α/β,15-dihydroxy-2,20-bise                          thyl-13-trans-prostenoic acid                             1743  1235           8α-methyl-9α/β,15-dihydroxy-2,20-bis                          ethyl-8-iso-13-trans-prostenoic acid                      1744  1236           8β-methyl-9α/β,15-dihydroxy-2,20-bise                          thyl-13-cis-prostenoic acid                               1745  1237           8α-methyl-9α/β,16-dihydroxy-2,20-bis                          ethyl-8-iso-13-cis-prostenoic acid                        1746  1238           8β-methyl-9α/β,15-dihydroxy-3-oxa-16,                          16-dimethyl-13-trans-prostenoic acid                      1747  1239           8α-methyl-9α/β,15-dihydroxy-3-oxa-16                          ,16-dimethyl-8-iso-13-trans-prostenoic acid               1748  1240           8β-methyl-9α/β,15-dihydroxy-3-oxa-16,                          16-dimethyl-13-cis-prostenoic acid                        1749  1241           8α-methyl-9α/β,15-dihydroxy-3-oxa-16                          ,16-dimethyl-8-iso-13-cis-prostenoic acid                 1750  1242           8β-methyl-9α/β,15-dihydroxy-3-oxa-13-                          trans,17-cis-prostadienoic acid                           1751  1243           8α-methyl-9α/β,15-dihydroxy-3-oxa-8-                          iso-13-trans,17-cis-prostadienoic acid                    1752  1244           8β-methyl-9α/β,15-dihydroxy-3-oxa-13-                          cis,17-cis-prostadienoic acid                             1753  1245           8α-methyl-9α/β,15-dihydroxy-3-oxa-8-                          iso-13-cis,17-cis-prostadienoic acid                      1753  1245           8α-methyl-9α/β,15-dihydroxy-3-oxa-8-                          iso-13-cis,17-cis-prostadienoic acid                      1754  1246           8β-methyl-9α/β,15-dihydroxy-7-nor-20-                          methyl-13-trans-prostenoic acid                           1755  1247           8α-methyl-9α/β,15-dihydroxy-7-nor-20                          -methyl-8-iso-13-trans-prostenoic acid                    1756  1248           8β-methyl-9α/β,15-dihydroxy-7-nor-20-                          methyl-13-cis-prostenoic acid                             1757  1249           8α-methyl-9α/β,15-dihydroxy-7-nor-20                          -methyl-8-iso-13-cis-prostenoic acid                      1758  1250           8β-methyl-9α/β,15-dihydroxy-2-fluoro-                          17,17-dimethyl-13-trans-prostenoic acid                   1759  1251           8α-methyl-9α/β,15-dihydroxy-2-fluoro                          -17,17-dimethyl-8-iso-13-trans-prostenoic acid            1760  1252           8β-methyl-9α/β,15-dihydroxy-2-fluoro-                          17,17-dimethyl-13-cis-prostenoic acid                     1761  1253           8α-methyl-9α/β,15-dihydroxy-2-fluoro                          -17,17-dimethyl-8-iso-13-cis-prostenoic acid              1762  1254           8β-methyl-9α/β,15-dihydroxy-10a-homo-                          13-trans-prostenoic acid                                  1763  1255           8α-methyl-9α/β,15-dihydroxy-10a-homo                          -8-iso-13-trans-prostenoic acid                           1764  1256           8β-methyl-9α/β,15-dihydroxy-10a-homo-                          13-cis-prostenoic acid                                    1765  1257           8α-methyl-9α/β,15-dihydroxy-10a-homo                          -8-iso-13-cis-prostenoic acid                             1766  1258           8β-methyl-9α/β,15-dihydroxy-2-phenyl-                          20-methyl-13-trans-prostenoic acid                        1767  1259           8α-methyl-9α/β,15-dihydroxy-2-phenyl                          -20-methyl-8-iso-13-trans-prostenoic acid                 1768  1260           8β-methyl-9α/β,15-dihydroxy-2-phenyl-                          20-methyl-13-cis-prostenoic acid                          1769  1261           8α-methyl-9α/β,15-dihydroxy-2-phenyl                          -20-methyl-8-iso-13-cis-prostenoic acid                   1770  1262           8β-methyl-9α/β,15-dihydroxy-5-cis,13-                          trans,17-cis-prostatrienoic acid                          1771  1263           8α-methyl-9α/β,15-dihydroxy-8-iso-5-                          cis,13-trans,17-cis-prostatrienoic acid                   1772  1264           8β-methyl-9α/β,15-dihydroxy-5-cis,13-                          cis,17-cis-prostatrienoic acid                            1773  1265           8α-methyl-9α/β,15-dihydroxy-8-iso-5-                          cis,13-cis,17-cis-prostatrienoic acid                     1774  1266           8β-methyl-9α/β,15-dihydroxy-5-cis,13-                          trans-prostadienoic acid                                  1775  1267           8α-methyl-9α/β,15-dihydroxy-8-iso-5-                          cis,13-trans-prostadienoic acid                           1776  1268           8β-methyl-9α/β,15-dihydroxy-5-cis,13-                          cis-prostadienoic acid                                    1777  1269           8α-methyl-9α/β,15-dihydroxy-8-iso-5-                          cis,13-cis-prostadienoic acid                             1778  1270           8β-methyl-9α/β,15-dihydroxy-20-ethyl-                          5-cis,13-trans-prostadienoic acid                         1779  1271           8α-methyl-9α/β,15-dihydroxy-20-ethyl                          -8-iso-5-cis,13-trans-prostadienoic acid                  1780  1272           8β-methyl-9α/β,15-dihydroxy-20-ethyl-                          5-cis,13-cis-prostadienoic acid                           1781  1273           8α-methyl-9α/β,15-dihydroxy-20-ethyl                          -8-iso-5-cis,13-cis-prostadienoic acid                    ______________________________________                                    

EXAMPLES 1782-1815

Catalytic hydrogenation of the 13-trans-prostenoic acids or esters listed below in Table 44 by the procedure described in Example 699 furnishes the product prostanoic acids of the table.

                  TABLE 44                                                         ______________________________________                                               Starting 13-   Products                                                  Ex-                                                                            trans-prostenoic                                                                     8-methylprostanoic                                                       ample acid or ester of                                                                              acids or esters                                                 Example                                                                  ______________________________________                                         1782  1206           Methyl 8β-methyl-9α/β,15-dihydroxy-pr                          ostanoate                                                 1783  1207           Methyl 8α-methyl-9α/β,15-dihydroxy-8                          -iso-prostanoate                                          1784  1210           Ethyl 8β-methyl-9α/β,15-dihydroxy-16,                          16-dimethyl-prostanoate                                   1785  1226           Decyl 8β-methyl-9α/β,15-dihydroxy-20-                          methyl-prostanoate                                        1786  1655           8β-methyl-9-oxo-15-dihydroxy-prostanoic acid         1787  1656           8α-methyl-9-oxo-15-dihydroxy-8-iso-prostanoic                            acid                                                      1788  1659           8β-methyl-9α/β,15-dihydroxy-prostanoi                          c acid                                                    1789  1660           8α-methyl-9α/β,15-dihydroxy-8-iso-pr                          ostanoic acid                                             1790  1678           8β-methyl-9-oxo-15-hydroxy-7a,7b-bishomo-prostan                          oic acid                                                  1791  1683           8α-methyl-9-oxo-15-hydroxy-2,20-bisethyl-8-iso-                          prostanoic acid                                           1792  1686           8β-methyl-9-oxo-15-hydroxy-3-oxa-16,16-dimethyl-                          prostanoic acid                                           1793  1694           8β-methyl-9-oxo-15-hydroxy-7-nor-20-methyl-prost                          anoic acid                                                1794  1702           8β-methyl-9-oxo-15-hydroxy-10a-homo-prostanoic                            acid                                                      1795  1523           8β-methyl-9α/β,15-trihydroxy-prostano                          ic acid                                                   1796  1524           8α-methyl-9α/β,15-trihydroxy-8-iso-p                          rostanoic acid                                            1797  1527           8β-methyl-9α/β,11α,15-trihydrox                          y-16,16-dimethyl-prostanoic acid                          1798  1531           8β-methyl-9α/β,11α,15-trihydrox                          y-17,17-dimethyl-prostanoic acid                          1799  1539           8β-methyl-9α/β-11α,15-trihydrox                          y-20-ethyl-prostanoic acid                                1800  1552           8α-methyl-9α/β,11α,15-trihydro                          xy-7a,7b-bishomo-8-iso-prostanoic acid                    1801  1551           8β-methyl-9α/β,11α,15-trihydrox                          y-7a,7b-bishomo-prostanoic acid                           1802  1555           8β-methyl-9α/β,11α,15-trihydrox                          y-2-ethyl-prostanoic acid                                 1803  1559           8β-methyl-9α/β,11α,15-trihydrox                          y-3,3,20-trimethyl-prostanoic acid                        1804  1563           8β-methyl-9α/β,11α,15-trihydrox                          y-3-oxa-prostanoic acid                                   1805  1567           8β-methyl-9α/β,11α,15-trihydrox                          y-3-oxa-16,16-dimethyl-prostanoic acid                    1806  1587           8β-methyl-9α/β,11α,15-trihydrox                          y-7a-homo-16,16-dimethyl-prostanoic acid                  1807  1643           Ethyl 8β-methyl-9α/β,11α,15                              trihydroxy-3-oxa-17,17-dimethyl-prostanoic acid           1808  1816           8β,15-dimethyl-9α/β,15-dihydroxy-pros                          tanoic acid                                               1809  1817           8β,15-dimethyl-9-oxo-15-hydroxy-prostanoic                                acid                                                      1810  1819           8α,15-dimethyl-9-oxo-15-hydroxy-8-iso-prostanoi                          c acid                                                    1811  1834           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-prostanoic acid                                    1812  1835           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-pros                          tanoic acid                                               1813  1837           8α,15-dimethyl-9-oxo-11α,15-dihydroxy-8-i                          so-prostanoic acid                                        1814  1843           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-7a,7                          b-bishomo-prostanoic acid                                 1815  1849           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-3-ox                          a-prostanoic acid                                         ______________________________________                                    

EXAMPLES 1816-1859

Treatment by the procedure described in Example 1082 of the 8-methyl-9α/β,15-dihydroxy-prostenoic acids listed in Table 45 below successively with 2,3-dichloro-5,6-dicyanobenzoquinone to give the corresponding 15-keto derivatives; 2.4 equivalents each of triethylamine and trimethylsilyl chloride to give the corresponding 9α/β-O-trimethylsilyl ether trimethylsilyl prostenoate ester in the instance of the 11α-hydroxy derivatives an additional 1.1 equivalent each of triethylamine and trimethylsilyl chloride is used and the 11α-O-trimethylsilyl ether derivative is obtained); methyl magnesium bromide to give the 15-methyl-15-hydroxy bis or tris trimethylsilyl blocked ether-ester; methanol-water-acetic acid for deblocking of the trimethylsilyl ether and ester blocking groups to give the listed 9α/β-hydroxy-15-methyl-15-hydroxy derivatives. In the 11-deoxy series treatment of these 9α/β-hydroxy-15-methyl-15-hydroxy products with Collins reagent in methylene chloride provides the corresponding 11-deoxy-9-oxo-15-hydroxy-15-methyl-prostenoic acids, also listed in the table. In the 11α-hydroxy series, treatment of the 9α/β,11α -15-trihydroxy-15-methyl derivatives with 1.1 molar equivalents each of triethylamine and trimethylsilyl chloride provides the corresponding 11α-O-trimethylsilyloxy-9α/β,15-dihydroxy derivative, which on oxidation in the usual way with Collins reagent in methylene chloride followed by silyl ether cleavage (treatment with methanol-water-acetic acid by the procedure described in Example 1082) provides the corresponding 9-oxo-11α,15-dihydroxy-15-methyl-prostenoic acids of the Table.

                  TABLE 45                                                         ______________________________________                                         Ex-   Starting 9α/β, (or                                            ample 9α),15-dihydroxy-                                                                       Product                                                         or 9α/β (or 9α),                                                             8,15-dimethyl-15-hy-                                            11α,15-trihydroxy                                                                       droxy-prostanoic                                                derivative of  acids                                                           Example                                                                  ______________________________________                                         1816  1659           8β,15-dimethyl-9α,β,15-dihydroxy-13-t                          rans-prostenoic acid                                      1817  1659           8β,15-dimethyl-9-oxo-15-hydroxy-13-trans-prosten                          oic acid                                                  1818  1660           8α,15-dimethyl-9α,15-dihydroxy-8-iso-13-t                          rans-prostenoic acid                                      1819  1660           8α,15-dimethyl-9-oxo-15-hydroxy-8-iso-13-trans-                          prostenoic acid                                           1820  1730           8β,15-dimethyl-9α/β,15-dihydroxy-13-t                          rans,17-cis-prostadienoic acid                            1821  1730           8β,15-dimethyl-9-oxo-15-hydroxy-13-trans-17-cis-                          prostadienoic acid                                        1822  1731           8α,15-dimethyl-9α/β,15-dihydroxy-8-i                          so-13-trans,17-cis-prostandienoic acid                    1823  1731           8α,15-dimethyl-9-oxo-15-hydroxy-8-iso-13-trans,                          17-cis-prostadienoic acid                                 1824  1738           8β,15-dimethyl-9α,β,15-dihydroxy-7a,7                          b-bishomo-13-trans-prostenoic acid                        1825  1738           8β,15-dimethyl-9-oxo-15-hydroxy-7a,7b-bishomo-13                          -trans-prostenoic acid                                    1826  1746           8β,15-dimethyl-9α/β,15-dihydroxy-3-ox                          a-16,16-dimethyl-13-trans-prostenoic acid                 1827  1746           8β,15-dimethyl-9-oxo-15-hydroxy-3-oxa-16,16-dime                          thyl-13-trans-prostenoic acid                             1828  1750           8β,15-dimethyl-9α/β,15-dihydroxy-3-ox                          a-13-trans,17-cis-prostadienoic acid                      1829  1750           8β,15-dimethyl-9-oxo-15-hydroxy-3-oxa-13-trans,1                          7-cis-prostadienoic acid                                  1830  1770           8β,15-dimethyl-9α/β,15-dihydroxy-5-ci                          s,13-trans,17-cis-prostatrienoic acid                     1831  1770           8β,15-dimethyl-9-oxo-15-hydroxy-5-cis,13-trans,1                          7-cis-prostatrienoic acid                                 1832  1778           8β,15-dimethyl-9α/β,15-dihydroxy-20-e                          thyl-5-cis,13-trans-prostadienoic acid                    1833  1778           8β,15-dimethyl-9-oxo-15-hydroxy-20-ethyl-5-cis,1                          3-trans-prostadienoic acid                                1834  1523           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-13-trans-prostenoic acid                           1835  1523           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-13-t                          rans-prostenoic acid                                      1836  1524           8α,15-dimethyl-9α/β,11α,15-tri                          hydroxy-8-iso-13-trans-prostenoic acid                    1837  1524           8α,15-dimethyl-9-oxo-11α,15-dihydroxy-8-i                          so-13-trans-prostenoic acid                               1838  1535           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-13-trans,17-cis-prostadienoic acid                 1839  1535           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-13-t                          rans,17-cis-prostadienoic acid                            1840  1539           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-20-ethyl-13-trans-prostenoic acid                  1841  1539           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-20-e                          thyl-13-trans-prostenoic acid                             1842  1551           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-7a,7b-bishomo-13-trans-prostenoic acid             1843  1551           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-7a,7                          b-bishomo-13-trans-prostenoic acid                        1844  1555           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-2-ethyl-13-trans-prostenoic acid                   1845  1555           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-2-et                          hyl-13-trans-prostenoic acid                              1846  1559           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-3,3,20-trimethyl-13-trans-prostenoic acid          1847  1559           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-3,3,                          20-trimethyl-13-trans-prostenoic acid                     1848  1563           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-3-oxa-13-trans-prostenoic acid                     1849  1563           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-3-ox                          a-13-trans-prostenoic acid                                1850  1571           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-3-oxa-13-trans-7-cis-prostadienoic acid            1851  1571           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-3-ox                          a-13-trans,17-cis-prostadienoic acid                      1852  1599           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-5-cis-13-trans-prostadienoic acid                  1853  1599           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-5-ci                          s,13-trans-prostadienoic acid                             1854  1603           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-5-cis,13-trans,17-cis-prostatrienoic acid          1855  1603           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-5-ci                          s,13-trans,17-cis-prostatrienoic acid                     1856  1611           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-4-nor-20-methyl-5-cis,13-trans-prostadienoic                            acid                                                      1857  1611           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-4-no                          r-20-methyl-5-cis,13-trans-prostadienoic acid             1858  1623           8β,15-dimethyl-9α/β,11α,15-trih                          ydroxy-4a,4b-bishomo-5-cis,13-trans,17-cis-prostatrie                          noic acid                                                 1859  1623           8β,15-dimethyl-9-oxo-11α,15-dihydroxy-4a,4                          b-bishomo-5-cis,13-trans,17-cis-prostatrienoic            ______________________________________                                                              acid                                                 

EXAMPLES 1860-1876

Treatment of the 8,15-dimethyl-9-oxo-11α-hydroxy derivatives listed in Table 46 below with aqueous acetic acid by the procedure described in Example 1387 is productive of the corresponding 10-prostenoic acid products of the table.

                  TABLE 46                                                         ______________________________________                                         Ex-   Starting 8,15-di-                                                        ample methyl-9-oxo-11α-                                                                       Product                                                   hydroxy deriva-                                                                      8,15-dimethyl-9-oxo-                                                           tives of Example                                                         10-prostenoic acid                                                             ______________________________________                                         1860  1835           8β,15-dimethyl-9-oxo-15-hydroxy-10,13-trans-pros                          tadienoic acid                                            1861  1837           8α,15-dimethyl-9-oxo-15-hydroxy-8-iso-10,13-tra                          ns-prostadienoic acid                                     1862  1839           8β,15-dimethyl-9-oxo-15-hydroxy-10,13-trans,17-c                          is-prostatrienoic acid                                    1863  1841           8β,15-dimethyl-9-oxo-15-hydroxy-20-ethyl-10,13-t                          rans-prostadienoic acid                                   1864  1843           8β,15-dimethyl-9-oxo-15-hydroxy-7a,7b-bishomo-10                          ,13-trans-prostadienoic acid                              1865  1845           8β,15-dimethyl-9-oxo-15-hydroxy-2-ethyl-10,13-tr                          ans-prostadienoic acid                                    1866  1847           8β,15-dimethyl-9-oxo-15-hydroxy-3,3,20-trimethyl                          -10,13-trans-prostadienoic acid                           1867  1849           8β,15-dimethyl-9-oxo-15-hydroxy-3-oxa-10,13-tran                          s-prostadienoic acid                                      1868  1851           8β,15-dimethyl-9-oxo-15-hydroxy-3-oxa-10,13-tran                          s,17-cis-prostatrienoic acid                              1869  1853           8β,15-dimethyl-9-oxo-15-hydroxy-5-cis,10,13-tran                          s-prostatrienoic acid                                     1870  1855           8β,15-dimethyl-9-oxo-15-hydroxy-5-cis,10,13-tran                          s,17-cis-prostatetraenoic acid                            1871  1857           8β,15-dimethyl-9-oxo-15-hydroxy-4-nor-20-methyl-                          5-cis,10,13-trans-prostatrienoic acid                     1872  1859           8β,15-dimethyl-9-oxo-15-hydroxy-4a,4b-bishomo-5-                          cis,10,13-trans,17-cis-prostatetraenoic acid              1873  1812           8β,15-dimethyl-9-oxo-15-hydroxy-10-prostenoic                             acid                                                      1874  1815           8β,15-dimethyl-9-oxo-15-hydroxy-3-oxa-10-prosten                          oic acid                                                  1875  1814           8β,15-dimethyl-9-oxo-15-hydroxy-7a,7b-bishomo-10                          -prostenoic acid                                          1876  1813           8α,15-dimethyl-9-oxo-15-hydroxy-8-iso-10-proste                          noic acid                                                 ______________________________________                                    

EXAMPLE 1877 Preparation of 3-methoxy-1-octyne

To an ice-cooled solution of 63 g. of 1-octyn-3-ol in 300 ml. of dimethoxyethane is added under an inert atmosphere 312 ml. of 1.6 M n-butyllithium in hexane dropwise over 1 hour. To the mixture is then added 145 g. of methyl iodide and the resulting mixture is stirred at ambient temperatures for 24 hours and then heated to 60°C. for 1 hour. The mixture is cooled and poured into cold dilute hydrochloric acid. The organic phase is separated, washed with water and saturated brine, dried (Na₂ SO₄), and evaporated to an oil, dried (Na₂ SO₄), and evaporated to an oil. Fractional distillation of the oil in vacuo yields the product as a colorless oil.

EXAMPLE 1878 Preparation of 1-Iodo-3-methoxy-trans-1-octene

Treatment of 3-methoxy-1-octyne (Example 1877) with disiamylborane, trimethylamine oxide, sodium hydroxide and iodine by the procedure described in Example 996 furnishes the title product.

EXAMPLE 1879 Preparation of 3-Methoxy-trans-1-octenyl lithium

Treatment of 1-iodo-3-methoxy-trans-1-octene (Example 1878) with butyl lithium in the manner of Example 961 pro provides a toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1880 Preparation of Lithium (3-methoxy-trans-1-octenyl)trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to the method of Example 963 from a hydrocarbon solution of 3-methoxy-trans-1-octenyl lithium(Exa (Example 1879) and trimethylaluminum.

EXAMPLES 1881-1895

Treatment of the cycloalkenones listed in Table 47 with lithium(3-methoxy-trans-1-octenyl)trimethylalanate (Example 1880) by the procedure described in Example 957 with the omission of the 80% aqueous acetic acid treatment (80°C., 1 hour) followed by saponification of the intermediate alkyl prostenoates by the procedure described in Example 122 furnishes the product 9-oxo-15-methoxy-13-trans-prostenoic acids of the table.

                  TABLE 47                                                         ______________________________________                                         Ex-   Starting cyclo-                                                                               Product 9-oxo-15-                                         ample alkenone of                                                              methoxy-13-trans-                                                                    Example                                                                  prostenoic acid                                                                ______________________________________                                         1881  23             9-oxo-7a,7b-bishomo-15-methoxy-13-trans-prostenoic                             acid                                                      1882  31             9-oxo-2-ethyl-15-methoxy-13-trans-prostenoic acid         1883  41             9-oxo-3,3-dimethyl-15-methoxy-13-trans-prostenoic                              acid                                                      1884  46             9-oxo-3-oxa-15-methoxy-13-trans-prostenoic acid           1885  53             9-oxo-7-nor-15-methoxy-13-trans-prostenoic acid           1886  70             9-oxo-2-fluoro-15-methoxy-13-trans-prostenoic acid        1887  74             9-oxa-7a-homo-15-methoxy-13-trans-prostenoic acid         1888  79             9-oxo-2-phenyl-15-methoxy-13-trans-prostenoic acid        1889  99             9-oxo-2-methyl-15-methoxy-13-trans-prostenoic acid        1890  111            9-oxo-10a-homo-15-methoxy-13-trans-prostenoic acid        1891  118            9-oxo-3-thia-15-methoxy-13-trans-prostenoic acid          1892  900            9-oxo-15-methoxy-5-cis,13-trans-prostadienoic acid        1893  1144           9-oxo-4-nor-15-methoxy-13-trans-prostadienoic acid        1894  1145           9-oxo-4-homo-15-methoxy-5-cis,13-trans-prostadienoic                           acid                                                      1895  1146           9-oxo-4a,4b-bishomo-15-methoxy-13-trans-prostadienoic                           acid                                                     ______________________________________                                    

EXAMPLES 1896-1910

Treatment of the 9-oxo-15-methoxy-13-trans-prostenoic acids listed in Table 48 below with lithium perhydro-9b-boraphenalylhydride by the procedure described in Example 737 furnishes the 9α-hydroxy-15-methoxy-13-trans-prostenoic acids of the Table.

                  TABLE 48                                                         ______________________________________                                               Starting 9-oxo-                                                          Ex-                                                                            15-methoxy-13-                                                                       Product 9α-hydroxy-15-                                             ample                                                                          trans-prosten-                                                                 methoxy-13-trans-                                                                    oic acid of                                                              prostenoic acid                                                                      Example                                                                  ______________________________________                                         1896  1881           9α-hydroxy-7a,7b-bishomo-15-methoxy-13-trans-pr                          ostenoic acid                                             1897  1882           9α-hydroxy-2-ethyl-15-methoxy-13-trans-prosteno                          ic acid                                                   1898  1883           9α-hydroxy-3,3-dimethyl-15-methoxy-13-trans-pro                          stenoic acid                                              1899  1884           9α-hydroxy-3-oxa-15-methoxy-13-trans-prostenoic                           acid                                                     1900  1885           9α-hydroxy-7-nor-15-methoxy-13-trans-prostenoic                           acid                                                     1901  1886           9α-hydroxy-2-fluoro-15-methoxy-13-trans-prosten                          oic acid                                                  1902  1887           9α-hydroxy-7a-homo-15-methoxy-13-trans-prosteno                          ic acid                                                   1903  1888           9α-hydroxy-2-phenyl-15-methoxy-13-trans-prosten                          oic acid                                                  1904  1889           9α-hydroxy-2-methyl-methoxy-13-trans-prostenoic                           acid                                                     1905  1890           9α-hydroxy-10a-homo-15-methoxy-13-trans-prosten                          oic acid                                                  1906  1891           9α-hydroxy-3-thia-15-methoxy-13-trans-prostenoi                          c acid                                                    1907  1892           9α-hydroxy-15-methoxy-5-cis,13-trans-prostenoic                           acid                                                     1908  1893           9α-hydroxy-4-nor-15-methoxy-5-cis,13-trans-pros                          tadienoic acid                                            1909  1894           9α-hydroxy-4-homo-15-methoxy-5-cis,13-trans-pro                          stadienoic acid                                           1910   1895β    9α-hydroxy-4a,4b-bishomo-15-methoxy-13-trans-pr                          ostenoic acid                                             ______________________________________                                    

EXAMPLE 1911 Preparation of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol

A solution of 5.0 g. (35 mmoles) of 5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (isomeric mixture; E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 25 ml. of DMSO is added during 0.5 minutes at 20°C. to a stirred solution of the Withig reagent [E. J. Corey et al., JACS, 91 5675 (1969); also Example 1108] and dimsyl sodium prepared from 23.5 g. (53 mmoles) of 4-carboxybutyltriphenylphosphonium bromide, 6.1 g. (140 mmoles) of 57% sodium hydride dispersion, and 230 ml. of DMSO (dimethylsulfoxide).

The solution is stirred at ambient temperatures for 2 hours and poured into a stirred mixture of methylene chloride, ice, and hydrochloric acid. The reaction mixture is worked up as described in Example 1105, and the crude product is purified by dry column chromatography on silica gel to provide the title compound (mixture of two stereoisomers) as an oil, IR (film) 3450, 1710, and 832 cm.sup.⁻¹.

EXAMPLE 1912 Preparation of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

A stirred solution of 2.98 g. (13.2 mmoles) of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example 1911) in 66 ml. of acetone is treated dropwise with 3.30 ml. of 8N chromic acid in 8N M₂ SO₄ during 20 minutes at -10 to -5°C. The solution is stirred at -5°C. for 10 minutes and treated successively with a few drops of isopropanol and 12 ml. of water. The mixture is filtered, and the filtrate is concentrated saturated with sodium chloride, and extracted with ethyl acetate. The extract is washed with brine, dried over MgSO₄, and evaporated to give an oil, IR (film) 1740, 1710, and 840 cm.sup.⁻¹.

EXAMPLE 1913 Preparation of 2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of (pH or 10.2-10.5) of 2.42 g. (10.8 mmoles) of 2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example 1912) 4.58 g. (43.2 mmoles) of sodium carbonate, and 216 ml. of water is allowed to stand at room temperatures under nitrogen for 24 hours. The solution is acidified at 15°C. with hydrochloric acid and extracted with ethyl acetate. The extract is washed with brine, dried over MgSO₄, and evaporated to give an oil; IR (film) 1700 (carbonyl groups) and 1630 cm.sup.⁻¹ (conjugated olefin); NMR 7.11 (1), 5.54 (2), and 4.95 (1)δ. 

We claim:
 1. Compounds of the formula: ##EQU22## wherein R' is an alkyl group having from 1 to 10 carbon atoms which may be different when t is greater than one; R is selected from the group consisting of a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups having from one to three carbon atoms, a straight chain alkenylmethyl group having from 3 to 10 carbon atoms and a straight chain alkenylmethyl group having from 3 to 10 carbon atoms and substituted with one or two alkyl groups having between them 2 to 5 carbon atoms; W is selected from a group consisting of lower alkyl, triphenylmethyl, triphenylmethyl in which one or two of the phenyl rings is substituted with a lower alkoxy group, tetrahydropyranyl, α-(lower alkoxy) substituted lower alkyl and tri(lower alkyl)silyl; s is an integer having the value of one to three, inclusive, and t is an integer having the values of one to three, inclusive, with the proviso that the sum of s and t must be equal to four.
 2. The compound according to claim 1 wherein s is one, t is three, R is n-pentyl, R' is methyl, and W is triphenylmethyl; lithium trimethyl 3-triphenylmethoxy-1-trans-octenyl alanate.
 3. The compound according to claim 1 wherein s is one, t is three, R is cis-2-pentenyl, R' is methyl, and W is triphenylmethyl; lithium trimethyl 3-triphenylmethoxy-1-trans,5-cis-octadienyl alanate.
 4. Compounds of the formula: ##EQU23## wherein R is lower alkyl; R° is lower alkyl; and R' is selected from the group consisting of a straight chain alkyl group having from 2 to 10 carbon atoms, a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with one or two alkyl groups having from one to three carbon atoms, a straight chain alkenylmethyl group having from 3 to 10 carbon atoms and a straight chain alkenylmethyl group having from 3 to 10 carbon atoms and substituted with one or two alkyl groups having between them 2 to 5 carbon atoms.
 5. The compound according to claim 4 wherein R and R° are methyl and R' is n-pentyl; lithium 3-triphenylmethoxy-1-trans-octenyl diisobutylmethyl alanate.
 6. The compound according to claim 4 wherein R and R° are methyl and R' is n-butyl; lithium 3-triphenylmethoxy-1-trans-heptenyl diisobutylmethyl alanate.
 7. The compound according to claim 4 wherein R and R° are methyl and R' is n-hexyl; lithium 3-triphenylmethoxy-1-trans-nonenyl diisobutylmethyl alanate.
 8. The compound according to claim 4 wherein R and R° are methyl and R' is cis-2-pentenyl; lithium 3-triphenylmethoxy-5-cis-1-trans-octadienyl diisobutylmethyl alanate.
 9. The compound according to claim 4 wherein R and R° are methyl and R' is 1-ethyl-n-pentyl; lithium-3-triphenylmethoxy-4-ethyl-1-trans-octenyl diisobutylmethyl alanate. 